Secondary Metabolites, Biological Activities, and Industrial and Biotechnological Importance of Aspergillus sydowii
by
,
Sabrin R. M. Ibrahim
1,2,*
,
Shaimaa G. A. Mohamed
3,
Baiaan H. Alsaadi
4,
Maryam M. Althubyani
4,
Zainab I. Awari
5,
Hazem G. A. Hussein
6,
Abrar A. Aljohani
7,
Jumanah Faisal Albasri
8,
Salha Atiah Faraj
9 and
Gamal A. Mohamed
10 1
Preparatory Year Program, Department of Chemistry, Batterjee Medical College, Jeddah 21442, Saudi Arabia
2
Department of Pharmacognosy, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt
3
Faculty of Dentistry, British University, El Sherouk City, Cairo 11837, Egypt
4
Department of Clinical Service, Pharmaceutical Care Services, King Salman Medical City, MOH, Al Madinah Al Munawwarah 11176, Saudi Arabia
5
Pharmaceutical Care Services, King Salman Medical City, MOH, Al Madinah Al Munawwarah 11176, Saudi Arabia
6
Preparatory Year Program, Batterjee Medical College, Jeddah 21442, Saudi Arabia
7
Pharmaceutical Care Services, Medina Cardiac Center, MOH, Al Madinah Al Munawwarah 11176, Saudi Arabia
8
Pharmacy Department, Home Health Care, MOH, Al Madinah Al Munawwarah 11176, Saudi Arabia
9
Pharmacy Department, King Salman Medical City, MOH, Almadinah Almunawarah 11176, Saudi Arabia
10
Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia
*
Author to whom correspondence should be addressed.
Mar. Drugs 2023, 21(8), 441; https://doi.org/10.3390/md21080441
Submission received: 11 July 2023
/
Revised: 29 July 2023
/
Accepted: 2 August 2023
/
Published: 5 August 2023
(This article belongs to the Special Issue Bioactive Secondary Metabolites of Marine Fungi)
Abstract
:Marine-derived fungi are renowned as a source of astonishingly significant and synthetically appealing metabolites that are proven as new lead chemicals for chemical, pharmaceutical, and agricultural fields. Aspergillus sydowii is a saprotrophic, ubiquitous, and halophilic fungus that is commonly found in different marine ecosystems. This fungus can cause aspergillosis in sea fan corals leading to sea fan mortality with subsequent changes in coral community structure. Interestingly, A. sydowi is a prolific source of distinct and structurally varied metabolites such as alkaloids, xanthones, terpenes, anthraquinones, sterols, diphenyl ethers, pyrones, cyclopentenones, and polyketides with a range of bioactivities. A. sydowii has capacity to produce various enzymes with marked industrial and biotechnological potential, including α-amylases, lipases, xylanases, cellulases, keratinases, and tannases. Also, this fungus has the capacity for bioremediation as well as the biocatalysis of various chemical reactions. The current work aimed at focusing on the bright side of this fungus. In this review, published studies on isolated metabolites from A. sydowii, including their structures, biological functions, and biosynthesis, as well as the biotechnological and industrial significance of this fungus, were highlighted. More than 245 compounds were described in the current review with 134 references published within the period from 1975 to June 2023.
1. Introduction
Fungi have so far received substantial attention for enhancing value in agricultural, industrial, pharmaceutical, and health fields [1,2,3,4]. During the past few decades, there have been some extremely intriguing advances in the utilization of fungi for new processes, products, and solutions that are crucial for the world. Also, fungi are proven to be a prolific pool of structurally varied bioactive metabolites. Additionally, fungal enzymes have been utilized instead of chemical processes in various industries, including those of textiles, leather, paper, pulp, animal feed, baked goods, beer, wine, and juice, which greatly reduces negative environmental effects [5]. Genus Aspergillus (Moniliaceae) is one of the most valuable fungal genera of commercial, biotechnological, and medicinal importance [6,7,8]. It comprises 400 species and attracts remarkable interest as a wealthy pool of structurally varied metabolites, including terpenoids, alkaloids, peptides, xanthones, and polyketides [7,8,9]. These metabolites have diverse bioactivities such as antibacterial, cytotoxic, antifungal, and anti-HIV activities.
Aspergillus sydowii is a saprotrophic, ubiquitous, and halophilic fungus and represents one of the widely distributed Aspergillus species [10,11,12]. It is commonly found in different habitats all over the world, including diverse soil and marine ecosystems, and possesses a broad range of salinity tolerance [13]. Interestingly, halophilic A. sydowii is employed as a model organism for investigating filamentous fungi’s molecular adaptation to hyperosmolarity [13]. A. sydowii can survive as a food contaminant, as a soil-decomposing saprotroph, and as an opportunistic human pathogen [14]. It causes onychomycosis and aspergillosis in humans, as well as aspergillosis in sea fan corals, on the basis of Koch’s postulate and physiological, morphological, and nucleotide sequence analyses [15,16,17]. Aspergillosis symptoms involve small necrotic lesions of tissues with purple halos, like the pathology of coral bleaching [18]. This leads to sea fan mortality and subsequent changes in coral community structure [18]. It was reported to cause 20–90% mortality in sea fans in the Florida Keys [18].
In addition to its pathogenic potential, A. sydowii has captured a considerable number of researchers’ attention due to its capacity to create a variety of biotechnologically and industrially significant enzymes, such as lipases, α-amylases, xylanases, cellulases, tannases, and keratinases [19,20,21,22,23]. Additionally, A. sydowii biosynthesizes various classes of metabolites, such as sesquiterpenoids, alkaloids, xanthones, monoterpenes, anthraquinones, sterols, triterpenes, diphenyl ethers, pyrones, cyclopentenones, anthocyanins, and polyketides [11,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38]. These metabolites have drawn remarkable interest because of their prominent bioactivities, including antioxidant, immunosuppression, antiviral, anti-mycobacterial, antimicrobial, cytotoxic, anti-inflammation, protein tyrosine phosphatase 1B (PTP1B) inhibition, anti-nematode, anti-diabetic, and anti-obesity properties [32,34,37,39,40,41,42,43,44,45,46,47,48]. Further, this fungus is employed for the synthesis of different types of nanoparticles that could have beneficial pharmaceutical, biotechnological, and industrial applications [49,50,51,52]. Recently, the number of articles on A. sydowii metabolites and their biotechnological and industrial relevance has risen substantially. It is noteworthy that a review paper discussing A. sydowii, particularly the positive aspects of this commercially useful fungus, was not found. Therefore, the current work provided a comprehensive and close insight into this fungus. The published information on the secondary metabolites identified from this fungus and their bioactivities were compiled. Additionally, the research on A. sydowii, including applications in industry, biotechnology, and nanotechnology, has been reviewed. Studies published in the literature within the period from 1975 to 2023 were reported. Additionally, the documented biosynthesis routes of the fungus’ major metabolites were illustrated.
Searches were conducted in depth on literature databases, namely PubMed, Web of Science, and Scopus, as well as on various websites of publishers (Wiley Online Library, Taylor & Francis, Springer, JACS, Thieme, and Bentham) and scientific websites (Google Scholar, PubMed, and ScienceDirect). The following phrases and keywords were used for the search: “Aspergillus sydowii,” “Aspergillus sydowii + compounds,” “Aspergillus sydowii + metabolites,” “Aspergillus sydowii + NMR,” “Aspergillus sydowii + biological activity,” “Aspergillus sydowii + Enzymes,” “Aspergillus sydowii + biotechnology,” “Aspergillus sydowii + biotechnological importance,” and “Aspergillus sydowii + nanoparticles”.
2. Secondary Metabolites of Aspergillus sydowii
2.1. Sesquiterpenes
Phenolic bisabolane sesquiterpenoids are among the main constituents reported from this fungus. They are a rare class of terpenes that have a p-alkylated benzene connected with 1C and 8C side chains at C-5 and C-2, respectively. Their structural variability is due to cyclization, reduction, or oxidation at various alkyl chain carbons to yield carboxylic acid, alcohol, lactone, double bond, pyran, and furan functionalities. Besides their fascinating skeletons, they show various bioactivities. It is noteworthy that most of the reported bisabolanes were separated from marine-derived A. sydowii as discussed below (Table 1).
In 1978, Hamasaki and his group separated and characterized compounds 1 and 2 as optically inactive metabolites from A. sydowii acetone extract by spectral and chemical means. These compounds were soluble in saturated NaHCO3 and positively reacted with bromophenol blue [11] (Figure 1).
Aspergillusene D (16) with a 7S-configuration was reported as a new sesquiterpenoid from Phakellia fusca-associated A. sydowii SCSIO-41301 by Liu et al., along with compounds 1, 5 8, 9, 10, and 22 that were characterized based on spectral and ECD (electronic circular dichroism) analyses [35]. Xu et al. separated compound 17, along with compounds 1, 8, and 23, from A. sydowii CUGB-F126 isolated from the Bohai Sea, Tianjin, using SiO2 (silica gel)/Sephadex LH-20/HPLC (high-performance liquid chromatography). Compound 17 is a new sydonic acid analog with a glycinate moiety [15].
Sun et al. developed a new approach that integrated computational programs (MS (mass spectrometry)-DIAL and MS-FINDER) and web-based tools (MetaboAnalyst and GNPS) for the identification of A. sydowii–Bacillus subtilis coculture metabolites, wherein 25 biosynthesized metabolites were detected and purified by SiO2/ODS CC/HPLC. Among them, compounds 1, 2, 3, and 18–21 were characterized by spectral and CD (circular dichroism) analyses [58]. Further, Hu et al. separated and characterized new bisabolene-type sesquiterpenoids 24 and 25 as well as the known analogs 2 and 23 from A. sydowii EN-434 obtained from Symphyocladia latiuscula marine red alga using RP-18 (reversed phase-18)/SiO2 CC (silica gel column chromatography) and spectral and ECD data. Compounds 24 and 25 have 7S/8S and 7R*/10R* configurations, respectively [32]. Fourteen new phenolic bisabolanes with varied structures, labeled 28–41, were separated and characterized by Niu et al. from the deep-sea sediment-derived A. sydowii MCCC-3A00324 (Figure 2).
Compounds 28 and 29 are the first bisabolanes with a 6/6/6 tricyclic skeleton, whereas compound 30 features a novel seco-bisabolane with a rare dioxolane moiety, and compound 38 has an unusual methylsulfonyl moiety [57]. Trisuwan et al. purified—from A. sydowii PSUF154 isolated from gorgonian sea fan of genus Annella—new bisabolane-type sesquiterpenes 4, 42, and 43, along with 1. Compound 42 has 2-substituted 6-methyl-2-heptenyl and 1,2,4-trisubstituted benzene. Compound 43‘s benzofuran moiety results from the ether linkage of C-1 OH of the tri-substituted phenyl and 2-substituted 6-methyl-2-heptenyl moieties. Compound 4 is a methyl ether of compound 1 with a 7S configuration [56]. The first phenolic bisabolane sesquiterpene glycoside, β-D-glucopyranosyl aspergillusene A (44), was purified from sponge-derived A. sydowii [36] and assigned using spectral and chemical methods [36].
Chung et al. stated that the addition of 5-azacytidine (a DNA methyltransferase inhibitor) to the culture of marine sediment-derived A. sydowii obtained from Hsinchu, Taiwan, significantly promoted the production of various metabolites [54]. Investigation of the EtOAc (ethyl acetate) extract of 5-azacytidine-treated culture broth by SiO2 CC and HPLC yielded new bisabolane sesquiterpenoids 5, 46, and 47, along with 1, 42, 45, and 49, that were assigned based on spectral analyses. The S-configuration of compounds 5 and 46 was assigned using optical rotation comparison, whereas compound 46 ([α]D +1.87) is a methyl derivative of compound 45 ([α]D +7.2) and compound 5 ([α]D +3.9) is C-12 hydroxy analog of compound 1 ([α]D +23) (Figure 3). On the other hand, compound 47 is closely similar to the previously reported compound 8 except for the absence of the C-3 carboxylic group in compound 47 [54]. Compounds 5, 46, and 47 were proposed to be biosynthesized from farnesyl diphosphate (FPP) created from the addition of an IPP (isopentenyl diphosphate) unit to a GPP (geranyl diphosphate) (Scheme 1). Then, cyclization and folding of the carbon chain through an electrophilic attack on double bonds produced the bisabolane nucleus that then underwent a series of carboxylation, hydration, oxidation, and reduction to give compounds 5, 46, and 47 [54].
A new bisabolane sesquiterpenoid, compound 15, in addition to compounds 1, 7, 6, 42, 47, 49, 50, and 52, were purified from A. sydowii ZSDS1-F6 EtOAc extract using SiO2/Sephadex LH-20/RP-HPLC by Wang et al. [45]. Compound 51 is a new aromatic bisabolene-type sesquiterpenoid with 11S-configuration purified and characterized from the sea-derived A. sydowii SW9 [41]. In 2022, Liu et al. purified a rare iodine- and sulfur-containing derivative (7S)- 4-iodo-flavilane A (54) along with compound 53. Compound 54 is 4-iodinated analog of compound 53 and its absolute S-configuration was proven by ECD analysis [38]. Furthermore, three undescribed cuparene-type sesquiterpenes, labeled 56–58, were isolated from fermented cultured EtOAc extract of the sea sediment-derived A. sydowii MCCC-3A00324 using SiO2/RP-18/Sephadex LH-20 CC/HPLC and assigned using spectral and ECD analyses. They represent rare cuparene-type sesquiterpenoids having a C-10 keto group and were discovered for the first time from filamentous fungi [57].
2.2. Mono- and Triterpenoids and Sterols
In 2020, the chemical investigation of deep-sea sediment-isolated A. sydowii MCCC-3A00324 by Niu et al. led to the separation of new osmane-type monoterpenoids aspermonoterpenoids A (59) and B (60) by SiO2 CC/HPLC and their structures were determined by spectral, ECD, and specific rotation analyses (Table 2, Figure 4). Compounds 59 and 60 are the first osmane monoterpenes reported from fungi, whereas compound 59 features a novel skeleton, which is possibly derived after the cleavage of the cyclopentane ring and oxidation reaction of the osmane monoterpenoid. They have 4S and 4S/5R/6S configurations, respectively [60].
These metabolites were proposed to be biosynthesized from a GPP that underwent subsequent hydrolysis/oxygenation/cyclization to yield the monocyclic osmane monoterpenoid ring. Then, carbon–carbon bond cleavage of osmane gives intermediate I and its further oxygenation yields compound 59, whilst the osmane oxygenation forms compound 60 [60] (Scheme 2).
Zhang et al. purified and characterized compound 61, a new 29-nordammarane-type triterpenoid, in addition to its known analog, compound 62, from the marine-derived A. sydowii PFW1-13 [48]. Compound 61 is structurally similar to compound 62 with a 1,1,2-trisubstituted ethanol unit instead of a trisubstituted ethenyl unit, suggesting that compound 61 is a C24–C25 hydrated derivative of compound 62 [48]. Its configuration was assigned as 4S/5S/6S/8S/9S/10R/13R/14S/16S/17Z based on comparing its optical rotation (−118.9) with that of compound 62 (optical rotation −105.1) [48].
2.3. Xanthone and Anthraquinone Derivatives
Xanthones are commonly found in lichen, fungi, plants, and bacteria [61]. In fungi, xanthones are mostly derived from acetyl-CoA through a series of polyketide synthase-catalyzed chemical transformations [62]. These metabolites were found to demonstrate diverse bioactivities.
Compounds 69 and 71 were reported from the EtOAc extract of 5-azacytidine-treated A. sydowii culture broth [54]. Additionally, from liverwort Scapania ciliate-accompanied A. sydowii, new xanthone derivatives, labeled 72, 76, and 77, and known compounds 74 and 78 were isolated by SiO2/Sephadex LH-20 CC/HPLC and assigned by spectral data. Compounds 76 and 77 are examples of sulfur-containing xanthones; compound 77 has an additional acetyl group at C-13 and compound 72 features C-2-OH instead of the methylthio moiety as in compound 76 [63]. New hydrogenated xanthones, aspergillusones A (86) and B (87), along with compounds 69, 71, 73, 88, and 90, were purified from a strain associated with the gorgonian sea fan of the genus Annella by Trisuwan et al. Compound 86 is a 11-deoxy derivative of compound 88 with an optical rotation of −1.6 and the same C-7 and C-8 absolute configuration, whereas compound 87 is a 1-hydroxy analog of compound 90 with 7R/8R and −46.3 optical rotation (Figure 5) [56].
In 2019, Wang et al. purified two novel xanthones, labeled 70 and 79, along with the known xanthones 71, 72, 74, 86, 88, and 89 and quinones 91, 94, and 96, from seawater-derived A. sydowii C1-S01-A7 using SiO2/Sephadex LH-20/RP-18/HPLC; the compounds were elucidated by spectral analyses (Table 3). Compound 79 is similar to previously reported 2-hydroxyvertixanthone with an additional formyl moiety at C-6, whereas compound 70 is similar to compound 69 with one more acetyl group at C-12 [55].
The cultured EtOAc extract of A. sydowii SCSIO-41301 associated with Phakellia fusca provided new xanthones 80 and 81. Compound 80 is related to versicone A with 3-OH instead of the isopentene group in versicone A, while compound 81 has an additional 6-OCH3 group compared to compound 80 [35]. The new mycotoxin 6-methoxyl austocystin A (83) and the related known compound 82 were isolated from Verrucella umbraculum-associated A. sydowii SCSIO-00305 (Figure 6). Compound 83 is similar to compound 82 except for the presence of an additional C6-OCH3. Their 1′R/2S configuration was assigned based on X-ray analysis [24].
2.4. Alkaloids
Alkaloids have drawn considerable attention because of their unique structural features and varied bioactivities. Interestingly, alkaloids belonging to various classes were reported from A. sydowii.
From the culture broth of coral Verrucella umbraculum-accompanied A. sydowii SCSIO-00305, using bio-guided fractionation, a new indole diketopiperazine member, cyclotryprostatin E (101), and compounds 100, 102, and 117–123 were purified using RP-18 CC/HPLC and characterized by spectral data interpretation [31] (Figure 8). Compound 101 is similar to compound 100 bar the replacement of the tri-substituted double bond in compound 100 with an oxygen-bonded quaternary carbon; compound 117 possesses indolyl, piperazinyl, and 1,2-disubstituted phenyl groups [31].
In 2008, Zheng et al. purified new diketopiperazines 103–105 and a new oxaspiro [4.4]lactam-containing alkaloid, labeled 131, along with compounds 106–109, 111, 112, 130, and 140–143 from the EtOAc extract of A. sydowii PFW1-13 isolated from driftwood sourced from Baishamen beach, Hainan, China, using SiO2/Sephadex LH-20 CC/HPLC [48]. The configurations of compounds 103–105 and 131 were assigned based on NMR (nuclear magnetic resonance) and CD spectral analyses, and the specific rotation was 3S/12S/18S for compound 103 and 9S/12S for compounds 104 and 105, while compound 131 was identified as a 14-nor-derivative of compound 130 with 5S/8S/9R/10S/11S/12Z configuration [48].
Biosynthetically, compounds 103–105 were postulated to be generated through a mixed mevalonic acid/amino acid pathway. Compound 105 is generated from the oxidation of compound 107, which results from mevalonic acid, tryptophan, and alanine. A cyclo(Trp-Pro) is formed from proline and tryptophan and is further oxidized and methylated to produce ethoxylated cyclo(Trp-Pro). Then, the latter reacts with mevalonic acid to yield compound 104 and intermediate I. An intramolecular aldol reaction of intermediate I yields intermediate III, which is deoxygenated to produce compound 106. Additionally, the dehydrogenation of compound 106 gives compound 103 (Scheme 3).
Kaur et al. separated a new diketopiperazine dimer WIN 64821 (115) and the known compound 110 using SiO2 CC and RP-HPLC from the CH3OH/CH3CN extract of A. sydowii MSX-19583 obtained from spruce litter; the compounds were assigned by spectral and ECD analyses and Marfey’s Method (Table 4). Compound 115 is structurally similar to the ditryptophenaline reported in various Aspergillus species and derived from tryptophan and phenylalanine subunits [33].
A new quinazolinone alkaloid, labeled 124, as well as related alkaloid 125 and triazole analog 134 were separated and characterized from the mycelia EtOAc extract of seawater-derived A. sydowii SW9 using SiO2/Rp-18/Sephadex LH-20 CC and spectral analyses (Figure 9). Compound 124 is an acetyl derivative of 2-(4-hydroxybenzyl)quinazolin-4(3H)-one, previously reported from Cordyceps-associated Isaria farinose [41,66].
Acremolins are rare alkaloids with a 5/6/5 tricyclic core, possessing an imidazole moiety fused with a methyl guanine moiety. Interestingly, acremolins were reported from Aspergillus species Aspergillus sp. S-3-75 and SCSIO-Ind09F01 and A. sydowii SP-1 [40,67]. From the Antarctic A. sydowii SP-1, a new alkaloid acremolin C (128) along with compound 110 were separated using SiO2 CC/ODS/HPLC and characterized by spectral methods. Compound 128 is a regio-isomer of acremolin B previously reported by Tian et al. from the deep-sea-derived fungus Aspergillus sp. SCSIO and has a isopropyl group at C-2′ instead of C-1′ (Figure 10) [40,67]. In 2022, Niu et al. purified and characterized, from the deep-sea-derived A. sydowii MCCC-3A00324, a new acremolin alkaloid acremolin D (129) along with compounds 110, 126, 127, 135, and 136 using SiO2 CC/HPLC and spectral and ECD data. Compound 129 is closely related to compound 127 in that one CH3 group in 127 has been replaced by an acetoxy methylene group [65].
New hetero-spirocyclic γ-lactam analogs azaspirofurans A (132) and B (133) were separated from the marine sediment-derived A. sydowii D2-6 using SiO2/Sephadex LH-20 CC and were characterized based on spectral and chemical evidence (Figure 10). These compounds featured an ethyl furan ring linked to 1-oxa-7-azaspiro[4,4]non2-ene-4,6-dione core [43].
2.5. Phenyl Ether Derivatives
Phenyl ethers are a group of simple polyketides that are widely reported in various Aspergillus species and have shown significant bioactivities (Table 5).
A new biphenyl ether derivative diorcinolic acid (148) together with compounds 144–147, 152, and 153 were separated from marine sponge Stelletta sp.-associated A. sydowii (Figure 11). Compound 149 featured two ether-linked 1,3-dioxy-6-carboxy-5-methylphenyl units. It was assigned as dicarboxylated diorcinol (carboxylated orcinol‘s ether-linked dimer) [36]. Bioassay-guided separation of the East China Sea sediment-derived A. sydowii MF357 yielded new tris-pyrogallol ethers sydowiols A–C (166–168) and related bis-pyrogallol ethers 144 and 145 that were characterized based on detailed spectral analysis and symmetry considerations [37]. On the other hand, the LC–UV–MS-guided separation of EtOAc extract of China Sea-derived A. sydowii resulted in new diphenyl ethers 155–157 and 159–161 along with compounds 146, 147, 149, 150, 152, and 162–164 using SiO2/Sephadex LH-20 CC/HPLC; the compounds were assigned using spectral and chemical methods. Compounds 155 and 156 are rare glycosides, possessing a D-ribose moiety, whereas compound 157 has a D-glucose moiety [9].
2.6. Chromane and Coumarin Derivatives
Citrinin is a polyketide-derived mycotoxin that was first reported in Penicillium citrinum as lemon-yellow particles. Also, other species of Monascus, Penicillium, and Aspergillus genera are found to be capable of producing this toxin [68].
The coculture of two or more different microbes is a useful approach for activating silent biosynthetic genes to accumulate cryptic compounds. In this regard, an investigation on the EtOAc extract of a coculture of A. sydowii EN-534 and P. citrinum EN-535 obtained from the marine red alga Laurencia okamurai using SiO2/Sephadex LH-20/RP-18 CC/preparative TLC (thin-layer chromatography) resulted in the separation of new citrinin analogs 171 and 172, in addition to compounds 169, 170, and 173–176, that were characterized by spectral, optical rotation, ECD, and X-ray analyses (Table 6, Figure 13). Compounds 171 and 172 are a citrinin dimer and citrinin monomer, respectively. The configurations of compounds 171–173 were assigned as 3R/4S/2′R/3′S, 3R/4S/2′R, and 3′S/1S/3R/4S by X-ray and ECD analyses [69]. Further, asperentin B (178), a new asperentin analog, was obtained from the Mediterranean sea sediment-derived A. sydowii EN50, which is closely related to compound 177 but with an additional OH at C-6 [46]; it was proposed to be derived from the hydroxylation of PKS (polyketide synthase) precursor at the aromatic ring [46].
2.7. Pyrane, Cyclopentene, Cyclopropane, and Lactone Derivatives
Two new 2-pyrone derivatives 195 and 196 and a new cyclopentenone derivative 208 along with known analog 197 were isolated from the South China Sea gorgonian Verrucella umbraculum-derived A. sydowii SCSIO-00305 utilizing SiO2/RP-10/Sephadex LH-20 CC/HPLC (Figure 14). The 8R/8S/5S absolute configuration of compounds 195, 196, and 208 was established using Mosher’s method and ECD spectra [24]. Liu et al. separated pryan analogs 194 and 193 from A. sydowii SCSIO-41301 (Table 7) [35]. Two new pyrone derivatives, labeled 189 and 198, together with compounds 199 and 200 were separated from Aricennia marina-inhabiting A. sydowii #2B by SiO2/Sephadex LH-20 CC/HPLC. Based on X-ray analysis and optical rotation measurement, compound 189 has 1S-configuration, while compounds 198 and 200 are racemic mixtures. Compounds 198 and 200 are alpha-pyrone derivatives; however, compound 189 is γ-pyrone [64]. Further, two undescribed α-pyrone derivatives 191 and 201 were separated and characterized from deep-sea-derived A. sydowii MCCC-3A00324. Compound 201 bears two phenyl moieties at C-3 and C-5 [60].
The cyclopropyl moiety is the smallest cycloalkane moiety. It is a strained moiety that usually occurs as a structural subunit of various natural metabolites, particularly alkaloids, steroids, and terpenoids [71,72]. Many polycyclic natural metabolites bearing this ring were reported in higher plants, archaea, fungi, and bacteria, while monocyclic molecules are rarely found [73]. In 1920, the first monocyclic cyclopropane (+)-trans-chrysanthemic acid was reported [42]. In 2022, sydocyclopropanes A–D (203–206), novel monocyclic cyclopropane acids, along with compound 207 were separated from the deep-sea sediment-associated A. sydowii MCCC-3A00324 using SiO2 CC/Sephadex LH-20/HPLC and were characterized by spectral, ECD, and DP4+ probability analyses by Niu et al. [42]. These metabolites feature a 1,1,2,3-tetrasubstituted cyclopropane moiety with different alkyl side chains. Their established configurations were 1S/2S/3S/12R for compound 203, 1S/2S/3S for compounds 204 and 205, and 1S/2R/3S for compound 206, which was identified as a C-2 epimer of compound 205 [42].
In 2006, Teuscher et al. separated and characterized new hydroxylated, chlorinated diaryl cyclopentenone derivatives 210 and 211 from red alga Acanthophora spicifera-associated A. sydowii using Sephadex LH-20/HPLC and NMR/CD analyses, respectively. These kinds of metabolites were related to diaryl cyclopentenones reported in order Boletales basidiomycetic fungi and involved in conspicuous bluing reactions of fruiting bodies and reported for the first time from ascomycetes [53]. Compound 215 was isolated as enantiomers, involving (+)-(215a) and (−)-(215b), using SiO2/RP-18 CC/HPLC from Rhododendron mole-accompanied A. sydowii and elucidated by spectral and CD analyses. They were purified by chiral HPLC and identified to have 7S and 7R configurations, respectively [26].
2.8. Other Metabolites
New catechol derivatives 223 and 224 were separated as racemic by Liu et al. and could not be separated into their enantiomers. Compound 224 resembles compound 223, except for the presence of the C-2 COOH group and a 2-methylpentan-1-ol unit, instead of the 2-CH3 and propionic acid moiety in compound 223 [35] (Table 8, Figure 15). A new chorismic acid analog, labeled 217, was reported by Liu et al. and its 3R/4S/5R/1′S configuration was assigned based on ECD analysis [41]. The same group separated a dibenzofuran derivative, labeled 234, from A. sydowii SCSIO-41301 [35]. Compounds 228–230 and 234 were separated by Niu et al. from the deep-sea sediment-associated A. sydowii MCCC-3A00324 [60].
Anthocyanins belong to the flavonoids family and are generally reported from plant sources. These metabolites have various applications in agro-food industries such as in natural dyes; additionally, their substantial therapeutic human health in treating obesity and improving cardiovascular function are of note [74]. In 2020, Bu et al. reported the capacity of A. sydowii H-1 to produce anthocyanins using metabolomic and transcriptomic analyses [25]. Compounds 242–246 were characterized; compounds 242 and 244 were the most abundant of the identified anthocyanins [25]. Interestingly, cinnamate-4-hydroxylase and chalcone synthase genes were identified as the key genes involved in anthocyanin biosynthesis [25]. This expanded the knowledge of natural anthocyanin biosynthesis by fungi for the first time.
3. Biological Activities of A. sydowii Extracts and Its Metabolites
3.1. Cytotoxic Activity
A. sydowii MSX19583 extract (%cell viability: 54%, conc.: 20 μg/mL) had moderate cytotoxic capacity against MDA-MB-435 (human melanoma cell line) in an MTT assay [33], while a cultured EtOAc extract displayed a marked toxic effect (LD50 (lethal dose 50) 36 μg/mL) in a brine shrimp assay [36].
Vascular endothelial cell growth factor (VEGF) is a tumor-secreted protein that stimulates both the migration and growth of vascular endothelial cells; thus, interference with VEGF signaling suppresses tumor growth or blocks angiogenesis [34].
Compound 88 was found to suppress HUVEC (human umbilical vein endothelial cell) proliferation caused by VEGF, bFGF (basic fibroblast growth factor), or ECGS (endothelial cell growth supplement) (IC50s: 1.4, 2.8 μM, and 6.2 μM, respectively) compared to SU5416 (a tyrosine kinase inhibitor, IC50s: 0.05, 5.3, and 30.5 μM, respectively) [34] and demonstrated selective cytotoxic capacity versus A549 (human lung adenocarcinoma epithelial cell line) (IC50 < 10 µM) [55].
In an MTT assay, compounds 101 and 117 demonstrated a notable cytotoxic capacity toward A375 (human melanoma cell line) (IC50: 5.7 μM), whereas compound 101 had no cytotoxicity towards adenocarcinoma cells A549, A375, and Hela (human cervical epitheloid carcinoma cell line) compared to cis-platin [31] and compounds 1, 45, 110, and 115 were inactive against MDA-MB-435 and HT-29 (human colon cancer cell lin) [33] (Table 9).
Acremolin D (129) had cytotoxic efficacy versus K562 (human erythroleukemic) and Hela-S3 (human cervix adenocarcinoma) cell lines with % inhibition equal to 25.1 and 30.6%, respectively, while compound 127 displayed activity (% inhibition: 20.9–35.5%) versus HepG2 (human hepatocellular liver carcinoma cell line), A549, and K562 in an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay [65]. Azaspirofurans A (132) displayed moderate cytotoxic potential versus A549 cell proliferation (IC50: 10 µM) in the MTT method [43] and compounds 103–105 (IC50s: 8.29, 1.28, and 7.31 µM, respectively) demonstrated weak capacities [48].
Compounds 44 and 149 were mildly active versus KB (human oral epidermoid carcinoma cell line), HepG2, and HCT-116 (human colon cancer cell line) cells (IC50s: 50–70 μM) compared to doxorubicin (IC50s: 5–6 μM) [36]. Wang et al. reported that compounds 146, 149, 152, 155, 160, and 161 were found to exhibit cytotoxic potential versus A549, U937 (pro-monocytic, human myeloid leukaemia cell line), HL-60 (human promyelocytic leukemia cell line), and K562 cells (IC50: 3.36–23.03 µM) [9]. Wang et al. stated that compounds 98, 99, 199, 200, and 216 possessed cytotoxic capacities versus VCaP (human prostate cancer cell line) (IC50s: 1.92–33.36 μM), but compound 189 was inactive in comparison with docetaxel (IC50: 4.95 nM) in the MTT method [64]. Compounds 83, 195, 196, and 208 possessed toxicity towards brine shrine nauplii (LC50s: 2.9–19.5 µM), whereas compound 83 had a potent efficacy (LC50: 2.9 µM) compared to toosendanin (LC50: 2.2 µM) [24]. On the other hand, compounds 192 and 239 revealed powerful cytotoxic potential versus P388 (menogaril-resistant mouse leukaemia cell line) (IC50s: 0.14 and 0.59 µM, respectively) in a SRB (sulforhodamine B) assay; however, compound 237 was inactive [44].
3.2. Antioxidant and Immunosuppression Activities
Compound 24 was found to have DPPH (1,1-diphenyl-2-picrylhydrazyl) scavenging activity (IC50: 113.5 μM/L), while compound 25 was inactive (IC50 value > 300 μM/L) compared to BHT (butylated hydroxytoluene) (IC50: 30.8 μM/L) in a DPPH assay, suggesting that the OH position and racemization influenced the activity [32]. Also, compound 88 demonstrated antioxidant capacity (IC50: 17.0 μM) compared to butylated hydroxyanisole (IC50: 0.13 μM). Compound 88 differed from compound 71 in lacking C7–C8 double bonds, revealing that the planar structure of compound 71 might reduce its activity [56]. On the other hand, compounds 195 and 196 had more potent antioxidant activity (IC50s: 46.0 and 46.6 µM, respectively) than L-ascorbic acid (IC50: 61.0 µM); however, compounds 83 and 208 were weakly active (IC50s: 98.0 and 86.3 µM, respectively) [24].
Compounds 72, 74, 76–78, 91, 94, 97, 218, and 220 were evaluated in vitro for immunosuppression capacity against Con-A (concanavalin A)- and LPS (lipopolysaccharide)-induced mouse splenic lymphocyte proliferation. It was noted that compounds 91 and 94 displayed moderate potential (IC50s: 8.45 and 10.10 μg/mL and 10.25 and 14.10 μg/mL, respectively), compared to cyclosporin A (IC50: 0.62 μg/mL for Con-A and 0.53 μg/mL for LPS). Other compounds showed weak or no activity [63].
3.3. Anti-Mycobacterial, Anti-Microalgal, and Antimicrobial Activities
Infectious illnesses seriously threaten human health worldwide [75,76]. Recently, the increasing recurrence of pathogens’ resistance to antimicrobials represents an alarming trend in infectious diseases that results from misuse or overuse of existing antimicrobials and has become a universal health concern [75,76].
A. sydowii ethyl acetate extract (conc.: 500 µg/disk) had selective activity against B. subtilis and E. coli (inhibition zone diameters (IZDs) 12 and 15 mm, respectively); however, it was inactive against S. aureus, C. albicans, Cladosporium herbarum, and C. cucumerinum [53]. In another study, the EtOAc extract of Dactylospongia sp.-associated A. sydowii DC08 revealed antibacterial potential versus E. coli and S. aureus (IZDs 12.31 and 14.25 mm, respectively) [77]. Wang et al. reported that A. sydowii ZSDS1-F6 EtOAc extract displayed significant antimicrobial capacity versus Aeromonas hydrophila and Klebsiella pneumonia [45].
The antibacterial effectiveness of compounds 1, 2, 5, 11–14, 42, 43, and 55 versus phytopathogenic bacteria Ralstonia solanacarum and Pseudomonas syringae utilizing a broth microdilution method revealed that compound 5 had inhibition potential versus P. syringae (MIC (minimum inhibitory concentration): 32 µg/mL), whereas compounds 1, 14, and 43 were active versus R. solanacarum (MICs: 32 µg/mL) using the broth microdilution method [47] (Table 10). Further, compounds 11 and 14 inhibited Fusarium oxysporum spore germination (EC50s: 54.55 and 77.16 µg/mL, respectively), while compounds 1, 11, 14, and 43 inhibited Alternaria alternata spore germination (EC50s: 26.02–46.15 µg/mL), suggesting the possible use of bisabolane sesquiterpenoids as anti-phytopathogens [47]. Also, compound 44 revealed antibacterial efficacy versus the human pathogen S. aureus and fish pathogens S. iniae and V. ichthyoenteri [36]. Compounds 71, 88, and 91 showed weak potential against Vibrio rotiferianus (MICs: 16–33 µg/mL); however, compounds 69, 79, 86, 88, 91, and 219 were weakly active versus MRSA (methicillin-resistant Staphylococcus aureus) (MICs: 15–32 µg/mL) compared to erythromycin and chloramphenicol [55].
Compounds 2, 3, and 110 demonstrated notable antibacterial efficacy versus S. aureus, MRSA, S. epidermidis, and MRSE (MICs: 0.25–1.0 μg/mL) compared to trigecycline (MICs: 0.06–0.12 μg/mL); however, compound 128 displayed moderate-to-weak activity (MICs: 4–32 μg/mL) [40]. Compounds 42, 50, and 146 had moderate effectiveness versus K. pneumonia (MICs: 21.4, 10.7, and 21.7 μM, respectively); also, compounds 1 and 42 exhibited moderate activity against E. faecalis (MIC: 18.8 μM) and A. hydrophila (MIC: 4.3 μM), respectively, using an agar dilution method [45].
Compounds 53, 54, and 165 (conc.: 20 µg/disc) were found to prohibit the growth of bacteria (V. anguillarum, V. harveyi, V. parahaemolyticus, and V. splendidus) and harmful microalgae (P. micans and P. minimum) in a disc diffusion assay [38]. Pathogenic bacteria and harmful algal blooms pose substantial threats to marine aquaculture. Compounds 53 and 54 inhibited P. micans and P. minimum (IC50 ranging from 1.3 to 11 μg/mL), while compound 165 only had inhibitory efficacy against P. minimum (IC50: 5.2 μg/mL). Additionally, these compounds showed inhibition against Vibrio species (V. anguillarum, V. harveyi, V. parahaemolyticus, and V. splendidus) with IZDs ranging from 6.4 to 8.7 mm. The MICs for compounds 53 and 54 were 8 μg/mL against V. anguillarum and V. parahaemolyticus and 16 μg/mL against V. harveyi [38].
Compounds 61, 62, 130, and 131 displayed notable growth inhibition potential versus E. coli, B. subtilis, and M. lysoleikticus (MICs: 3.74–87.92 µM); compounds 131 and 61 were more powerful than compounds 62 and 130 [48]. Antibacterial testing of compounds 51, 124, 125, and 134 against human pathogenic bacterial strains E. coli, S. aureus, S. pneumoniae, and S epidermidis revealed that compounds 51, 124, and 125 demonstrated selective inhibitory capacities (MICs ranging from 2.0–16 μg/mL), whereas compound 51 had significant activity against E. coli (MIC: 2.0 µg/mL) that was comparable to chloramphenicol (MIC: 2.0 µg/mL) [41].
Among the pyrogallol ethers, i.e., compounds 144, 145, and 166–168 reported by Liu et al. in 2013, compounds 166 and 168 (IC50: 14.0 and 24.0 μg/mL, respectively) demonstrated Mt PtpA (protein tyrosine phosphatase A) (Mycobacterium tuberculosis protein tyrosine phosphatase A)-inhibitory activity and compound 168 moderately inhibited S. aureus (MIC: 12.5 μg/mL) [37]. M. tuberculosis secretes PtpA into the infected macrophages’ cytosol to avoid devastation by macrophage phagocytosis. Inhibition of PtpA remarkably attenuates M. tuberculosis growth in human macrophages; therefore, Mt PtpA is a target for developing anti-tuberculosis drugs [37].
Liu et al. stated that compounds 144–146, 152, and 153 were moderately effective versus fish pathogens S. iniae FP3187, and V. ichthyoenteri (Vi0917-1 and Vi099-7) and human pathogen S. aureus (SG 511 and SG 503) [36]. Compounds 147 and 149 were inactive, suggesting that methoxy groups increased the antibacterial potential; however, the carboxyl group reduced the activity of diphenyl ether derivatives [36]. Additionally, compounds 138, 139, 144, 209, and 210 possessed moderate antibacterial effectiveness (MICs: 6.3–25.0 µM) versus series of bacterial strains [28] and compound 84 was moderately active (MICs: 64, 128, 16, 32, and 32 µg/mL, respectively) versus MRSA, MDRPA (multi-drug-resistant Pseudomonas aeruginosa), E. coli, S. aureus, and P. aeruginosa in an agar diffusion assay [39].
Compounds 137, 169–172, 174–176, 221, and 222 reported from A. sydowii EN-534 and Penicillium citrinum EN-535 coculture were examined for antibacterial potential versus strains of human and aquatic bacteria. Compounds 137, 169, and 170 showed antibacterial capacity against bacteria E. coli, E. ictaluri, M. luteus, V. parahaemolyticus, and V. alginolyticus (MICs ranged from 4 to 64 μg/mL), while compounds 137, 171, 172, and 174 were active against V. alginolyticus and E. ictaluri (MICs: 32–64 μg/mL). Additionally, compound 170 had marked activity against M. luteus (MIC: 4 μg/mL) compared to chloramphenicol (MIC: 2 μg/mL) [69].
3.4. Anti-Influenza Virus Activity
The influenza pandemic remains a threat to public health because of its elevated rates of mortality and morbidity. Although vaccination is the primary means for preventing this illness, antiviral medications are an essential adjunct to vaccines for influenza control and prevention [78,79]. In the last several decades, natural products have been subjected to intensive investigations as a possible alternative therapy for the recovery and treatment of influenza. Various reports have demonstrated that developing natural bioactive metabolites has remarkable advantages [78,79]. It is noteworthy that the renowned anti-influenza oseltamivir was synthesized using natural shikimic and quinic acids as starting materials [78,79]. Some reports assessed the anti-influenza potential of A. sydowii-isolated metabolites; these are highlighted below (Table 11).
Interestingly, compounds 80 and 81 possessed notable selective inhibition versus two influenza A virus subtypes, including A/Puerto Rico/8/34 (H1N1) and A/FM-1/1/47 (H1N1) (IC50s: 2.17–4.70 μM), compared to ribavirin (IC50s: 2.53 to 6.23 μM). Additionally, compounds 92 and 94 had potent efficacy on A/Puerto Rico/8/34 (H1N1) (IC50s: 1.92 and 2.0 μM, respectively). Furthermore, compound 234 demonstrated broad inhibitory potential against A/Puerto Rico/8/34 (H1N1), A/Aichi/2/68 (H3N2), and A/FM-1/1/47 (H1N1) (IC50s: 1.31, 1.24, and 2.84 μM, respectively) compared to ribavirin (IC50s: 2.53, 6.23, and 3.97 μM, respectively) [35]. Compounds 50, 146, and 152 demonstrated weak anti-H3N2 potential (IC50s: 57.4, 66.5, and 78.5 μM, respectively) in a CPE (cytopathic effect) inhibition assay compared to Tamiflu (IC50: 0.95 μM) [45]. Further, Yang et al. stated that compounds 137, 169–172, and 174 demonstrated anti-influenza NA (neuraminidase) activity, with compounds 137 and 174 displaying better efficacy (IC50s: 12.9 nM and 18.5 nM, respectively) compared to oseltamivir (IC50: 3.6 nM) [69]. Additionally, compounds 203–207 demonstrated antiviral potential versus the A/WSN/33 virus (H1N1) (IC50s ranged from 26.7 to 77.2 μM), compared to oseltamivir (IC50: 18.1 μM); compounds 203, 204, and 207 were the most active (IC50s: 26.7, 29.5, and 35.8 µM, respectively). It was found that the C-1 methyl 2-hydroxy-4-oxobutanoate side chain significantly enhanced the antiviral activity (e.g., compound 203 vs. compound 205) and C-3 configuration had less influence on activity (e.g., compound 205 vs. compound 206) [42].
3.5. Anti-Diabetic and Anti-Obesity Activities
A close relation among between diabetes and obesity has been proven [80]. Insulin-triggered cellular glucose uptake is a crucial step in glucose regulation and any defect in this mechanism results in insulin resistance [81]. Enhancement of insulin sensitivity is one of the significant hallmarks of anti-diabetic agents. Lipid accumulation in diabetic patients can result in serious effects such as diabetic cardiomyopathy [82]. Hence, efficient anti-diabetics should decrease adipocytes’ lipid accumulation and facilitate lipid metabolism and burning [54].
In an anti-diabetic assay, compounds 1, 5, 42, 45, 46, 47, 49, 69, 71, and 88 were found to increase differentiated 3T3-L1 (fibroblast embryo mouse cell line) adipocytes’ medium glucose consumption. Among them, compound 45 significantly reduced culture medium glucose concentration (324.6 mg/dL) by 24% compared to control (glucose: 427.4 mg/dL). It was noted that the presence of a methylene alcohol and a hydroxy group on C-3 and C-7, respectively, in bisabolane sesquiterpenes is substantial in promoting 3T3-L1 adipocytes’ glucose uptake [54]. Additionally, their efficacy on differentiated 3T3-L1 adipocytes’ lipid accumulation utilizing oil-red O stain revealed that compound 45 notably prohibited lipid accumulation up to 48% in a 3T3-L1 adipocyte culture medium, indicating the compound 45 promoted glucose consumption and suppressed lipid accumulation in adipocytes [54].
3.6. Protein Tyrosine Phosphatase Inhibition
Protein tyrosine phosphatases (PTPs) are proven to be substantial new targets for new anti-diabetes [58]. For example, PTP1B (protein tyrosine phosphatase 1B) negatively regulates insulin action in the insulin receptor signaling pathway, SHP1 (SH2-containing protein tyrosine phosphatase 1) negatively controls signaling pathways, which streamlines glucose homeostasis through modulating insulin signaling in muscles and the liver, and CD45 (leukocyte common antigen) is a receptor for some ligands and regulates SHP-1 recruitment [58]. Also, PTP1B has a substantial role in cancer development, inflammation processes, and insulin signaling cascade. Therefore, PTP1B inhibitors are considered drug candidates for treating cancer, diabetes, inflammation processes, and sleeping sickness [46].
Asperentin B (178) had potent PTP1B inhibition capacity (IC50: 2.05 μM) compared to suramin (IC50: 11.85 μM). It was sixfold more potent than suramin, suggesting its possible application in anti-diabetes and anti-sleeping sickness therapeutic agents [46]. Furthermore, compounds 1, 3, and 18 displayed significant PTP1B-inhibitory potential (IC50s: 7.97, 15.88, and 14.18 μM, respectively), while compounds 1, 2, 18, and 240 had potent activity towards SHP1 (IC50s: 8.35, 15.72, 11.68, and 14.61 μM, respectively). The PTP1B data indicated that the side chains influenced activities [58].
3.7. Anti-Inflammation Activity
Compounds 42, 45, and 88 markedly inhibited fMLP (tripeptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine)/CB (cytochalasin B)-caused superoxide anion generation (IC50s: 5.23, 6.11, and 6.00 µM, respectively) and elastase release (IC50s: 16.39, 8.80, and 6.60 µM, respectively) by neutrophils [54]. It is noteworthy that compounds 1, 5, 46, and 49 had selective inhibition versus fMLP/CB-caused superoxide anion generation [54]. These results demonstrated the importance of C-7 OH (compound 45 vs. compound 46) and C-3 methylene alcohol (compounds 46, 45, and 49 vs. compounds 1 and 5) on activity (Table 12). On the other hand, compound 71 also revealed a significant superoxide anion generation inhibition capacity (IC50: 21.20 µM) compared to compound 69 [54]. The isolated metabolites, compounds 1–3, 26–42, 45, 47, 50, 56–58, and 214, showed a dose-dependent inhibition of LPS-induced NO (nitric oxide) secretion (conc.: 10 and 5 µM) in BV-2 microglia cells using a CCK-8 (cell counting kit-8) assay. Compounds 33, 39, 42, 47, 50, and 57 revealed an inhibition rate >45% (conc.: 10 µM). The structure–activity relation indicated that the Δ7,8 double bond in sydowic acid derivatives enhanced NO secretion inhibition (e.g., compound 33 vs. compound 26). Compound 39, with a 56.8% inhibition rate, was found to exert its anti-inflammation activity by prohibiting the NF-κB (nuclear factor kappa B)-activated pathway [57].
It was found that compounds 145 and 153 mildly suppressed NO production induced by LPS-NO in RAW 264.7 cells (IC50: 73 μM) compared to dexamethasone (IC50: 18 μM) [36]. Additionally, compounds 59, 60, 146, 152, 191, 201, 213, 228–230, and 234 demonstrated an inhibitory capacity of NO production induced by LPS in BV-2 microglia cells without toxicity according to a CCK-8 assay. Interestingly, compound 234 (10 µM) was the most potent (inhibition rate: 94.4%) among these tested compounds (inhibition rate: 10.2–35.4%) [60].
Compounds 98, 189, 199, and 200 possessed inhibitory effectiveness on LPS-boosted NO production in RAW264.7 cells (IC50s: 25.25–43.08 μM), compared to dexamethasone (IC50: 35.17 uM) [64]. Recently, Chen et al. reported that compounds 215 and 236 exhibited weak inhibition of LPS-induced NO production (20.1, 21.5, and 18.1%, respectively), compared to dexamethasone (% inhibition: 99.9%) in RAW 264.7 cells using a Griess reaction assay [26].
3.8. Anti-Nematode Activity
Globally, parasitic nematodes cause diseases of major socio-economic significance to humans and animals. They have a long-term impact on human health, especially in children [83]. Indeed, nematodes’ resistances to available anti-nematode agents are widespread all over the world [84]. Thus, there is an insistent demand to discover new agents for the effective and sustained control of nematodes.
Sun et al. evaluated the anti-nematode activity of compounds 1–3, 18–21, 202, 235, and 240. It is noteworthy that only compound 3 showed anti-nematode potential (IC50: 50 μM) [58]. A study by Yang et al. revealed that compounds 1, 11, and 14 possessed nematicidal potential versus second-stage juvenile Meloidogyne incognita (J2s); compound 1 had the strongest activity (% mortality: 80% at 60 and LC50: 192.40 µg/mL). Furthermore, compounds 1, 11, and 14 paralyzed the nematode and then impaired its pathogenicity [47].
4. Industrial and Biotechnological Applications
The discovery and development of effective enzymes for the use of renewable resources as raw materials is a requirement for the transition to a biobased economy. Many enzymes are crucial in efficiently hydrolyzing raw materials by enzymatic means. Exploring the potential of untapped natural habitats is a potent method for overcoming the limited enzymatic toolkit.
A. sydowii was found to be a rich source of enzymes with marked industrial and biotechnological potential, including α-amylases, lipases, xylanases, cellulases, keratinase, and tannases, which are discussed here.
4.1. α-Amylase, Tannases, and Lipase Enzymes
Amylases (AAs) are utilized in multiple manufacturing processes, including fermentation, textile, detergent, paper, and pharmaceutical sectors [85]. Given the low cost and wide availability of the starch feedstock used to make food, bioethanol, textile, paper, detergent, and chemicals, there is a significant demand for α-amylase [86]. However, because of advancements in biotechnology, the use of AAs has increased in a variety of sectors such as those of clinical, pharmaceutical, and analytical chemistry, as well as in the food, textile, and brewing industries [85]. The huge industrial demand for AAs to support economically competitive manufacturing processes is still being severely hampered by the cost and effectiveness of AA cocktails [19]. In this regard, it is imperative to generate effective and affordable AAs by using inexpensive sources such as agricultural wastes.
Adegoke and Odibo produced AAs from A. sydowii IMI-502692 utilizing the solid-state fermentation of buffered cassava root fiber. It was found that this activity was enhanced by Ca2+, Cu2+, and Zn2+; however, it was prohibited by Fe2+, Sr2+, Ni2+, and Mn2+ [19].
A study by Elwan et al. reported that A. sydowii had a potential for lipase production (lipase yield of 90 µ/mL) in optimum culture conditions, specifically 5.4 pH; 2.0% sucrose, 0.2% corn oil, 0.23% (NH4)2SO4, 0.1% KH2PO4, 0.05% MgSO4·7H2O, 0.05%KCl, and using 0.1 M phosphate–citrate buffer and incubating at 30°C for 20 h [22].
Tannase, an extracellular enzyme belonging to the hydrolase family, is derived from various species of the Aspergillus genus [8,87]. It catalyzes the breakdown of depsides and tannins. Tannase lessens tannins’ unwanted effects (astringent and bitter taste), enhancing the flavor qualities of products such as animal feeds and foodstuffs. It is used in various applications, including polyphenolic compound structural elucidation, bioremediating tannin-contaminated wastewaters, gallic acid production, and coffee-flavored soft drink, fruit juice, and instant tea production [20].
In 2020, Albuquerque et al. purified and characterized tannase-acyl hydrolase from A. sydowii SIS-25 derived from Caatinga soil (Serra Talhada, Pernambuco, Brazil) utilizing a polyethylene glycol-citrate aqueous two-phase system. This enzyme removed phenolic components and enhanced the sensory qualities of green tea and produced gallic acid [20].
4.2. Bioremediation and Biodegradation
Sustainable development goals (SDGs) target various concerns in our planet such as food security, health, environmental sustainability, bioremediation, climate change, alternative eco-friendly fuel, improving water quality, sustainable food production, and discovering new drugs [88]. Treatment and measurement of various contaminants in water, soil, and air are complicated issues and are linked to the nature of contaminants and their environmental interactions. Reusing wastewater offers a substitute supply for the irrigation of agricultural land that has been used for decades in many nations. Recycling wastewater adheres to circular economy principles by reducing waste and encouraging ongoing resource reuse [89] which potentially assists various national initiatives in promoting sustainable agriculture methods. Creating agricultural systems with minimal required inputs and zero waste contributes to SDG 2 (End hunger) (via sustainable food production), SDG 12 (Responsible consumption and production), SDG 13 (Climate action), and SDG 15 (Sustainable use of terrestrial ecosystems) [90]. Various researches have focused on biologically based methods, relying on natural processes to remove contaminants such as the utilization of microorganisms (bioremediation) such as fungi to remarkably contribute to achieving the SDGs [88].
4.2.1. Polycyclic Aromatic Hydrocarbons
PAHs (polycyclic aromatic hydrocarbons) are a heterogeneous class of hydrocarbons having two or more fused aromatic rings. In nature, they are formed as a result of organic matter’s incomplete decomposition and human activities such as petroleum spilling, waste incineration, home heaters, and the burning of carbon, oil, gas, or wood [91]. Additionally, PhCs (pharmaceutical compounds), a second class of contaminants, have become more significant in recent years as a result of their durability and abundance in surface water bodies and the ineffectiveness of treatment facilities eliminating them [92]. According to Olicón-Hernández et al., these contaminants are hazardous to aquatic life and contribute to microbial resistance’s emergence [93]. Numerous studies have focused on the microbial biodegradation of these contaminants, particularly by fungi [93,94], because these pollutants are known for their high toxicity and persistence [94]. It is noteworthy that halophilic fungi are useful in xenobiotic mycoremediation under high-salinity conditions [94].
González-Abradelo et al. studied the potential of A. sydowii EXF-12860 toward the bioremediation of saline wastewaters, containing toxic and persistent PAHs and PhCs. It was stated that A. sydowii may be helpful in lowering the amounts of harmful PAHs and PhCs under high-salinity conditions (>1 M NaCl) during the biotechnological downstream processing of diverse industrial wastewater. It removed 100% of fifteen complex PAHs at 500 ppm in biorefinery wastewater at high salt concentrations. Additionally, it has ecotoxic activity as it demonstrated the same capability to eliminate PhCs. This supported its capabilities for xenobiotic biodegradation in low-water activity [94]. A novel piezo-tolerant and hydrocarbon-oclastic deep-sea sediment-derived A. sydowii BOBA1 demonstrated a marked degradation potential for PAHs in spent engine oil hydrocarbon fractions (71.2 and 82.5% of spent engine oil, respectively) under high-pressure (0.1 and 10 MPa, respectively) culture conditions with a 21-day retention period. This provided insights into the bioremediation of hydrocarbon-contaminated deep-sea environments [95].
Additionally, Birolli et al. stated that A. sydowii CBMAI-935 isolated from a non-contaminated site on the coast of São Sebastião (Brazil) biodegraded anthracene [96]. To biodegrade dieldrin, one of the most widely employed organo-chlorine pesticides, banned due to its long persistence and high toxicity to the environment, Birolli et al. found that A. sydowii CBMAI-935 and A. sydowii CBMAI-933 were capable of growing in the presence of dieldrin, suggesting its high tolerance. It is noteworthy that no biodegradation byproducts were found in the GCMS, revealing that dieldrin could be converted into polar molecules or mineralized, prohibiting the emergence of harmful or durable derivatives [97].
4.2.2. Heavy Metals and Insecticides
Cadmium (Cd) is often used in the electroplating and metallurgical industries and is found in several pesticides, fertilizers, and fungicides [98]. Upon its absorption by both animals and humans, it accumulates in the kidneys and liver, severely harming the renal tubules and resulting in a variety of symptoms such as proteinuria and hyperglycemia [99]. Trichlorfon (TCF) is a broad-spectrum organic phosphorus pesticide that is utilized for controlling pests on a variety of crops [100]. It is an inhibitor of cholinesterase that causes delayed neuropathy in both animals’ and humans‘ nervous systems [98].
Zhang et al. reported that by inoculating A. sydowii into Cd-TCF co-contaminated soil, TCF breakdown was accelerated, and soil enzyme activity was raised. When Brassica juncea (Indian mustard) was planted along with A. sydowii inoculation, maximum TCF degradation and Cd removal efficacy were noted. Brassica juncea is among those hyperaccumulator plant species that are frequently employed for heavy metal phytoextraction from contaminated soil. Thus, using B. juncea and A. sydowii together is a promising strategy to bioremediate soil that has been contaminated with both TCF and Cd [98]. Tian et al. isolated PAF-2, a new strain of A. sydowii from pesticide-contaminated soils, that had potential for the biodegradation of TCF and its degradation [100].
Esfenvalerate (S,S-fenvalerate), is a pyrethroid insecticide that deposits in marine sediments and is extremely harmful to aquatic creatures. Birolli et al. examined its biodegradation by marine-associated A. sydowii CBMAI-935. This strain metabolized esfenvalerate into 3-phenoxybenzoic acid, 2-(4-chlorophenyl)-3-methylbutyric acid, and its dihydroxylated derivatives [101].
Alvarenga et al. assessed the biodegradation of a commercial formulation of chlorpyrifos (Lorsban 480 BR), which is one of the most widely utilized organophosphate pesticides, by marine-derived A. sydowii CBMAI-935 associated with C. erecta. The fungus degraded ≈ 63% of the chlorpyrifos and decreased the concentration of its hydrolysis product 3,5,6-trichloropyridin-2-ol after 30 days [102]. In 2021, Soares et al. reported that this fungus also metabolized chlorpyrifos and profenofos to 3,5,6-trichloro-1-methylpyridin-2(1H)-one/2,3,5-trichloro-6-methoxypyridine/tetraethyl dithiodiphosphate/3,5,6-trichloropyridin-2-ol and 4-bromo-2-chlorophenol/4-bromo-2-chloro-1-methoxybenzene/O,O-diethyl S-propylphosphorothioate, respectively [103].
Methyl parathion is an efficient organophosphate acaricide and insecticide that is widely utilized for pest control on a wide variety of crops, but it is extremely toxic. Alvarenga et al. reported the ability of A. sydowii CBMAI-935 to biodegrade this pesticide completely after 20 days. This fungus metabolized this pesticide to its more toxic isomerization and oxidation products isoparathion and methyl paraoxon, which were subsequently metabolized to the less toxic product 1-methoxy-4-nitrobenzene/p-nitrophenol/O,O,O-trimethyl phosphorothioate/O,O,S-trimethyl phosphorothioate/trimethyl phosphate, suggesting A. sydowii CBMAI-935’s efficiency in the bioremediation of this pesticide and its toxic forms [103,104].
4.2.3. Lignocellulosic Biomasses
Due to the acute energy crisis and increased demand for fossil fuels, lignocellulose is widely considered a potential cost-effective, renewable resource for bioethanol production [105,106]. Lignocellulose consists of cellulose, hemicellulose, and lignin. Lignin, which together with hemicellulose and cellulose makes up the majority of a plant’s skeleton, is the second-most abundant organic renewable resource on Earth after cellulose [105,106]. The ligninolytic enzymes Lac (laccase), LiP (lignin peroxidase), VP (versatile peroxidase), and Mnp (manganese peroxidase) play a major role in the breakdown of lignin [105,106] and are found among the extracellular enzymes in filamentous fungi. These enzymes play a significant role in bioremediation, as they neutralize or degrade contaminants in the environment [6]. They also have a wide range of uses in the paper, textile, cosmetic, food, chemical, agricultural, and energy industries.
A thermostable, low-molecular-weight xylanase belonging to the glycosyl hydrolase 11 family was purified from A. sydowii MG49 by Ghosh et al. and demonstrated specific efficacy only in the presence of xylan and had no activity in the presence of cellulose or carboxymethyl cellulose [23].
A. sydowii MS-19 isolated from the Antarctic region produced low-temperature lignin-degrading enzymes LiP and Mnp. These results suggested that A. sydowii MS-19 could be used as a source of lignocellulosic enzymes [107].
Xylan is the prime constituent of hemicellulose. Its backbone consists of a linear chain of 1,4-linked β-D-xylopyranosyl units, which are substituted with α-L-arabinofuranosyl, 4-O-methyl-α-D-glucuronopyranosyl, or acetyl units. It is degraded by β-D-xylosidases, endo-1,4-β-xylanases, α-glucuronidases, α-l-arabinofuranosidases, acetyl xylan esterases, and ferulic acid esterases [108].
Brandt et al. stated that A. sydowii Fsh102 isolated from shrimp shells showed notable xylanase-producing capacity [109]. Two xylanases I and II belonging to GH-11 (glycoside hydrolases) and GH-10 families, respectively, were characterized and expressed in E. coli. These enzymes can function in a wide pH range and are tolerant of mesophilic temperatures. Both xylanases can be characterized as being extremely interesting for the enzymatic breakdown of xylan-containing biomasses in industrial bioprocesses based on their activity and stability [109]. In another study on A. sydowii SBS-45 culture filtrate, two xylanases (I and II) were purified. They showed optimum activity at 50 °C and 10.0 pH. This activity was boosted by certain metal ions and L-tryptophan [110].
Cellulose breakdown is carried out by cellulases, including β-glucosidase, endoglucanase, and cellobiohydrolase [108,111,112]. Cellulase has wide applications in various fields like oil extraction, agricultural industries, food processing, waste management, carotenoid extraction, animal feed, brewery, textile, bio-stoning, color clarification, paper, laundry, pulp, detergent industry, and deinking [108,111,112].
A. sydowii isolated from Indore, India, had the potential to produce cellulases under submerged fermentation. It was found that β-glucosidase, exoglucanase, and endoglucanase were produced at a ratio of 64:27:9, whereas lactose was the best carbon source for inducing cellulase production [113].
4.2.4. Keratinous Wastes
Keratins are components of hooves, wool, horns, nails, hair, and feathers [8,114]. They are insoluble proteins with highly stable polypeptide chains, containing many disulfide bonds [115,116]. According to estimates, the United States, China, and Brazil produce 40 million tons of keratinous waste each year [117]. Also, keratinous waste is produced in millions of tons annually in meat industry slaughterhouses worldwide [115,116]. Normal enzymes such as papain and pepsin that break down proteins cannot break them down. Keratinous waste management utilizing a low-cost solution is needed particularly in underdeveloped nations. These wastes can be broken down by microbial keratinases which are extracellular enzymes secreted by various bacterial and fungal genera [8,114]. They are widely used in different pharmaceutical industries, in treating keratinized skin, calluses, acne, and psoriasis, and in cosmetic products manufacture (e.g., nutritional lotions, anti-dandruff shampoos, and creams) [21,115,116]. Also, they are usually employed in nitrogen fertilizers, feed formulas, and the leather industry, as well as in treating keratin waste-contaminated wastewater [21].
Alwakeel et al. studied the capability of keratinase produced by A. sydowii AUMC-10935 isolated from male scalp hair to degrade keratinous materials from chicken feathers. The enzyme had optimal activity (120 IU/mg) at 50 °C and pH 8.0, which was notably prohibited by EDTA and certain metal ions [21].
4.3. Biocatalysis
The pharmaceutical sector is continually looking for new approaches to new therapeutic agent syntheses, which has increased the demand for biocatalytic techniques [118]. Whole microorganism cells are effectively used as catalysts in the stereoselective biotransformation of a variety of chemical molecules. Also, many chemical reactions such as carbonyl ketone reduction, sulfide oxidation, secondary alcohol deracemization, and Baeyer–Villiger reactions were all catalyzed by enzymes from various microorganisms [6]. The whole cell of A. sydowii was investigated as a biocatalyst for various chemical reactions. This was highlighted in the current work.
Whole cells of the marine sponge-derived A. sydowii Gc12 obtained from the South Atlantic Ocean catalyzed the hydrolysis of (R,S)-benzyl glycidyl ether to produce (R)-benzyl glycidyl ether. Derivatives of glycidyl ether are potentially beneficial intermediates in the manufacture of β-adrenergic blockers. A. sydowii Gc12 hydrolases showed regioselectivity in opening the epoxide ring of racemic oxirane [119].
Sponge-associated A. sydowii CBMAI-934 derived from Chelonaplysilla erecta produced oxidoreductase that catalyzed regioselective mono-hydroxylation of (−)-ambrox® to 1β-hydroxy-ambrox. (−)-Ambrox®, a naturally occurring terpene, was separated from ambergris, a pathological substance formed in the blue whale’s intestine. This compound is of great commercial value in the perfume industry as a fixative or fragrant agent [120]. de Paula and Porto investigated progesterone biotransformation by A. sydowii CBMAI-935 associated with marine sponge Geodia corticostylifera. In a good yield, this fungus was able to oxidize progesterone at the C17-site, resulting in the two major products testololactone and testosterone. Additionally, this Baeyer–Villiger reaction-based bio-oxidation revealed the existence of crucial enzymes in this fungus that can aid in related steroid biotransformation [121]. A. sydowii CBMAI-935 only produced 2′,4-dihydroxy-dihydrochalcone with a yield of 26% from 2′,4-dihydroxy-dihydrochalcone [122].
Further research was conducted by de Oliveira et al. to assess the potential of A. sydowii CBMAI-934 isolated from the marine sponge Chelonaplysilla erecta in converting a number of methylphenylacetonitriles into corresponding acids at a high yield. It was found that aryl aliphatic nitrilases were induced by phenyl acetonitrile. Thus, A. sydowii CBMAI-934 might serve as a biocatalyst for the production of carboxylic acids from nitriles [123]. Zhou et al. reported that A. sydowii PT-2 isolated from Pu-erh tea degraded theobromine to 3-methylxanthine in a liquid culture through N-7 demethylation [124]. Also, Jimenez et al. reported that A. sydowii CBMAI 935 associated with C. erecta sponge collected from Sao Sebastiao, São Paulo, Brazil, enantioselectively reduced ene of E-2-cyano-3-(furan-2-yl)acrylamide to (R)-2-cyano-3-(furan-2-yl)propanamide with a high yield [125]. In 2018, Morais et al. studied the reduction of α-chloroacetophenones to (S)-alcohols using whole cells of marine-derived A. sydowii CBMAI 935 [126]. α-bromoacetophenones‘ biotransformation by the marine-derived A. sydowii Ce19 was studied by Rocha et al. in 2010 [127]. This fungus accelerated α-bromoacetophenones’ bioconversion into (R)-2-bromo-1-phenylethanol (56%), in addition to acetophenone (4%), 1-phenylethan-1,2-diol (26%), phenylethanol (5%) and α-chlorohydrin (9%). The substituted p-nitro- and p-bromoacetophenone’s biotransformation produced a low-concentration complex combination of breakdown products [127]. In 2017, Alvarenga and Porto tested the biocatalytic ability of A. sydowii CBMAI-935 of marine origin to convert 2-azido-1-phenylethanone and some derivatives to related alcohols for use in the synthesis of enantiomerically bioactive β-hydroxy-1,2,3-triazoles. A. sydowii CBMAI 935 displayed extremely high stereoselectivity and conversion values for the bio-reduction of 2-azido-1-phenylethanones to (S)-2-azido-1-phenylethanols [128]. Further, the marine-derived A. sydowii Ce15 converted 1-(4-methoxyphenyl)ethenone to (R)-1-(4-methoxyphenyl)ethanol [129].
5. Nanoparticle Synthesis
Nanoparticles (NP) have attracted great interest recently because of their apparent applications in different fields such as biosensors, biomedicine, cosmetics, drugs, photocatalysis, animal dietary supplements, biolabeling, etc. [130]. Conventional NP synthesis approaches are not environment-friendly and are cost-intensive. Therefore, the development of biocompatible, environment-friendly, and non-toxic protocols in nanostructure biosynthesis is a wealthy area for scientific research, wherein the use of microbes could be an auspicious alternative [131,132]. Fungi are more effective organisms for these purposes than other microbes because of their special features, including their greater growth capacity, greater potential to produce a variety of enzymes, richness in mycelial branching, ability to accumulate different metals, and capacity to grow in harsh environments [133].
A. sydowii derived from Bhavnagar coast water (Gulf of Khambhat, India) had a remarkable intra/extracellular capacity to biosynthesize gold nanoparticles with variable sizes depending on gold ion concentration [52]. Additionally, silver NPs were biosynthesized by Wang et al. using soil-derived A. sydowii culture supernatants. These NPs revealed an in vitro antiproliferative capacity against MCF-7 (human breast adenocarcinoma cell line) and HeLa cells and efficient antifungal potential versus various clinical pathogenic fungi [134].
Zhang et al. prepared magnetic chitosan microsphere-immobilized A. sydowii by utilizing the cross-linking of γ-Fe2O3 magnetic chitosan nanocomposites with A. sydowii through the instant gelation method. This microsphere demonstrated marked Cu adsorption capacity (19.21 mg/g) and good regeneration properties after four cycles, suggesting its potential application as a biosorbent for treating heavy metal-contaminated water [51].
The AgNPs synthesized by Nayak and Anitha from dune-associated A. sydowii had significant antimicrobial potential versus selected bacterial stains; its combination with vancomycin and ampicillin showed enhanced activity (by sevenfold against Shigella sp. and by sixfold against B. cereus and S. aureus [50]).
Organic waste and heavy metal removal from wastewater have always been a major concern for the environment. In order to simultaneously remove trichlorfon and cadmium from an aqueous solution, Zhang et al., in 2020, created magnetic chitosan beads-immobilized A. sydowii [49]. The beads demonstrated considerable trichlorfon and cadmium removal capabilities, as well as outstanding four-cycle recyclability. As a result, the beads are appropriate and efficient for removing cadmium and trichlorfon simultaneously from wastewater [49].
6. Conclusions
Fungi have been subjected to much research due to their significance as wealth generators for various enzymes and bio-metabolites, as well as being intriguing for applications in agricultural, industrial, and pharmaceuticals fields.
A. sydowii is a globally distributed fungus that was found to have the capacity to biosynthesize diverse classes of metabolites. In the current work, 246 metabolites were separated from A. sydowii in the period from 1975 to 2023 (Figure 16). Most of these metabolites were reported from 2017 to 2022.
These metabolites include sesquiterpenoids, alkaloids, xanthones, monoterpenes, anthraquinones, sterols, triterpenes, phenyl ethers, pyrones, cyclopentenones, anthocyanins, coumarins, chromanes, acids, phenols, and other metabolites. Sesquiterpenoids (58 compounds, 24%), phenyl ethers (25 compounds, 10%), alkaloids (44 compounds, 18%), and xanthones (22 compounds, 9%) are the major constituents reported from this fungus (Figure 17).
This fungus was collected from different sources such as cultures, plants, marine environments (water, sea mud, sediment, gorgonian sea fans, algae, sponge, and driftwood), and liverworts. Most of the reported studies were carried out on A. sydowii isolated from marine sources. It is remarkable that this fungus has many enzymatic systems, which may help to explain why its metabolites are so diverse. Future studies will be useful in understanding the enzymes and genes responsible for the manufacture of these metabolites.
It was found that the coculture of this fungus with other microbes, as well as the modification of the culture media, significantly promoted the production of structurally varied metabolites, suggesting avenues of further research using these approaches for activating A. sydowii’s silent biosynthetic genes toward the accumulation of various substantial compounds.
These metabolites were assessed for different bioactivities, including cytotoxic, antimicrobial, antioxidant, antiviral, anti-obesity, anti-inflammation, immunosuppression, anti-diabetic, protein tyrosine phosphatase 1B (PTP1B) inhibition, and anti-nematode activities (Figure 18).
Compounds 195 and 196 displayed potent antioxidant activity. Compounds 67, 187, 192, and 239 demonstrated powerful cytotoxic potential. Compounds 2, 3, and 110 had notable antibacterial efficacy. Compounds 80, 81, 92, 94, and 234 displayed potent anti-influenza virus activity. Furthermore, compound 45 was found to possess anti-diabetic and anti-obesity capacities through promoting glucose consumption and suppressing lipid accumulation, whereas compound 178 had a potent PTP1B inhibition capacity compared to suramin, suggesting its possible application in anti-diabetic and anti-sleeping sickness therapeutic agents.
Despite the large number of metabolites, biological evaluation has only been conducted for a limited number of them, mainly in vitro, and there is a lack of pharmacological investigations that focus on studying the possible action mechanisms of the active metabolites. Therefore, mechanistic and in vivo studies are recommended to clarify and validate potential mechanisms for the active metabolites. Moreover, studies on the structure–activity relationships of these metabolites should be carried out.
Additionally, molecular dynamic and docking studies could be employed to investigate the possible bioactivities of the untested metabolites.
On the other side, many of the tested metabolites displayed no notable effectiveness in some of the tested activities. Therefore, estimation of other possible bioactivities and molecular dynamic and docking studies, as well as derivatization of these metabolites, should clearly be the target of future research.
For further production of structurally varied metabolites by this fungus, cocultivation techniques should be considered an area for future investigation. In addition, exploring the biosynthetic pathways of these bio-metabolites is required and could enable the rational engineering or refactoring of these pathways for industrial purposes. Further, identification of the biosynthetic genes responsible for these metabolites may provide the opportunity to discover A. sydowii’s genetic potential for discovering novel metabolites by metabolic engineering, which could lead to more affordable and novel pharmaceutics.
According to the published reports, A. sydowii can produce diverse types of enzymes with potential biotechnological and industrial applications. Research that focuses on engineering enzymes in such a way for maximum activity and stability under appropriate conditions is desirable. Recombinant DNA technology and engineering of proteins are required to improve the industrial production of these enzymes. A. sydowii can withstand high-salinity conditions, pointing to its biotechnological and industrial relevance. It was proven that this fungus adsorbed heavy metals and degraded pesticides, agrochemicals, and contaminants. As a result, A. sydowii might serve as an environmentally safe tool for bioremediation and for converting hazardous materials into useful products. The minor reports described NP synthesis utilizing this fungus. These biosynthesized NPs possessed antiproliferative and antimicrobial potential as well as biosorbent capacity for treating heavy metal- and pesticide-contaminated water. However, the synthesized NPs using A. sydowii are limited to silver, γ-Fe2O3 magnetic chitosan nanocomposites, and chitosan beads-immobilized A. sydowii. Therefore, future research should focus on developing protocols for implementing the biosynthesis of other types of NPs such as carbides, metal oxides, and nitrides using this fungus and their bio-evaluation, which could be a promising area for more anticipated beneficial effects.
Despite the large number of published studies on A. sydowii, mycologists, biologists, and chemists still need to conduct more extensive research to fully understand the potential of this fungus and its secondary metabolites.
Author Contributions
Conceptualization, S.R.M.I., H.G.A.H. and G.A.M.; resources, B.H.A., M.M.A., Z.I.A., A.A.A., J.F.A., S.A.F., and S.G.A.M.; data curation, B.H.A., M.M.A., Z.I.A., A.A.A., J.F.A. and S.A.F.; writing—original draft preparation, S.R.M.I., S.G.A.M., H.G.A.H. and G.A.M.; writing—review and editing, B.H.A., M.M.A., Z.I.A., A.A.A., J.F.A. and S.A.F. All authors have read and agreed to the published version of the manuscript.
Funding
This research received no external funding.
Institutional Review Board Statement
Not applicable.
Informed Consent Statement
Not applicable.
Data Availability Statement
Not applicable.
Conflicts of Interest
The authors declare no conflict of interest.
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Figure 1.
Structures of sesquiterpenoids (1–21) reported from A. sydowii.
Figure 2.
Structures of sesquiterpenoids (22–41) reported from A. sydowii.
Scheme 1.
Biosynthetic pathway of compounds 5, 46, and 47: GPP: Geranyl diphosphate; FPP: Farnesyl diphosphate; IPP: Isopentenyl diphosphate [54].
Scheme 1.
Biosynthetic pathway of compounds 5, 46, and 47: GPP: Geranyl diphosphate; FPP: Farnesyl diphosphate; IPP: Isopentenyl diphosphate [54].
Figure 3.
Structures of sesquiterpenoids (42–58) reported from A. sydowii.
Figure 4.
Structures of mono- (59 and 60) and triterpenoids (61 and 62) and sterols (63–68) reported from A. sydowii.
Figure 4.
Structures of mono- (59 and 60) and triterpenoids (61 and 62) and sterols (63–68) reported from A. sydowii.
Scheme 2.
Biosynthetic pathway of compounds 59 and 60 [60].
Scheme 2.
Biosynthetic pathway of compounds 59 and 60 [60].
Figure 5.
Structures of xanthones (69–80) reported from A. sydowii.
Figure 6.
Structures of xanthones (81–90) reported from A. sydowii.
Figure 7.
Structures of quinones (91–99) reported from A. sydowii.
Figure 8.
Structures of alkaloids (100–117) reported from A. sydowii.
Scheme 3.
Biosynthetic pathway of compounds 103–106 [48].
Scheme 3.
Biosynthetic pathway of compounds 103–106 [48].
Figure 9.
Structures of quinazoline alkaloids (118–126) reported from A. sydowii.
Figure 10.
Structures of alkaloids (127–143) reported from A. sydowii.
Figure 11.
Structures of phenyl ether derivatives (144–157) reported from A. sydowii.
Figure 12.
Structures of phenyl ether derivatives (158–168) reported from A. sydowii.
Figure 13.
Structures of chromane and coumarin derivatives (169–192) reported from A. sydowii.
Figure 14.
Structures of pyrane, cyclopentene, cyclopropane, and lactone derivatives (193–216) reported from A. sydowii.
Figure 14.
Structures of pyrane, cyclopentene, cyclopropane, and lactone derivatives (193–216) reported from A. sydowii.
Figure 15.
Other metabolites (217–246) reported from A. sydowii.
Figure 16.
Number of metabolites reported from A. sydowii per year.
Figure 17.
Different classes of metabolites reported from A. sydowii. AnTs: anthocyanins; SQT: sesquiterpenes; MT: monoterpenes; OMs: other metabolites; PHs: phenols; TRT: triterpens; ST: sterols: XT: xanthones; QU: quinones; ALK: alkaloids; PhEs: phenyl ethers; CHs: chromanes; COs: coumarins; Pys: pyranes; CPEs cyclopentenes; CyPr: cyclopropane, and lactone derivatives.
Figure 17.
Different classes of metabolites reported from A. sydowii. AnTs: anthocyanins; SQT: sesquiterpenes; MT: monoterpenes; OMs: other metabolites; PHs: phenols; TRT: triterpens; ST: sterols: XT: xanthones; QU: quinones; ALK: alkaloids; PhEs: phenyl ethers; CHs: chromanes; COs: coumarins; Pys: pyranes; CPEs cyclopentenes; CyPr: cyclopropane, and lactone derivatives.
Figure 18.
Number of metabolites evaluated for each bioactivity.
Table 1.
Sesquiterpenoids reported from Aspergillus sydowii (molecular weight and formulae, strain, host, and location).
Table 1.
Sesquiterpenoids reported from Aspergillus sydowii (molecular weight and formulae, strain, host, and location).
| Compound Name | Mol. Wt. | Mol. Formula | Strain, Host, Location | Ref. |
|---|---|---|---|---|
| (+)-(7S)-Sydonic acid (1) | 266 | C15H22O4 | Cultured, IFO 7531, Japan | [11] |
| - | - | Acanthophora spicifera (red alga), Rameswaram, India | [53] | |
| Marine sediment, Hsinchu, Taiwan | [54] | |||
| - | - | CUGB-F126, seawater, Bohai Sea, Tianjin | [15] | |
| - | - | C1-S01-A7, seawater sample, West Pacific Ocean | [55] | |
| - | - | PSU-F154, genus Annella sp. (gorgonian sea fan), coastal area, Surat Thani, Thailand | [56] | |
| - | - | MSX19583, spruce litter, Colorado, USA | [33] | |
| - | - | ZSDS1-F6, unidentified marine sponge, Xisha Islands, China | [45] | |
| - | - | C1-S01-A7, seawater sample, West Pacific Ocean | [55] | |
| - | - | SCSIO 41301, Phakellia fusca (marine sponge), Xisha Islands, China | [35] | |
| - | - | MCCC 3A00324, deep-sea sediment, South Atlantic Ocean | [57] | |
| - | - | Deep-sea mud, Dalian, China | [58] | |
| - | - | CPCC 401353, cultured, China | [59] | |
| - | - | LW09, deep-sea sediment, Southwest Indian Ridge | [47] | |
| (7S)-(+)-Hydroxysydonic acid = Aspergoterpenin C (2) | 282 | C15H22O5 | Cultured, IFO 7531, Japan | [11] |
| - | - | Acanthophora spicifera (red alga), Rameswaram, India | [53] | |
| - | - | SP-1, marine sediment sample, Antarctic Great Wall Station | [40] | |
| - | - | EN-434, Symphyocladia latiuscula (red alga), Qingdao coastline, China | [32] | |
| - | - | MCCC 3A00324, deep-sea sediment, South Atlantic Ocean | [57] | |
| - | - | Piece of deep-sea mud, Dalian, China | [58] | |
| - | - | CPCC 401353, cultured, China | [59] | |
| - | - | LW09, deep-sea sediment, Southwest Indian Ridge | [47] | |
| (7S)-(−)-10-Hydroxysydonic acid (3) | 282 | C15H22O5 | Piece of deep-sea mud, Dalian, China | [58] |
| - | - | MCCC 3A00324, deep-sea sediment, South Atlantic Ocean | [57] | |
| - | - | CPCC 401353, cultured, China | [59] | |
| (+)-(7S)-7-O-Methylsydonic acid (4) | 280 | C16H24O4 | PSU-F154, genus Annella sp. (marine gorgonian sea fan), coastal area, Surat Thani, Thailand | [56] |
| (7S,11S)-(+)-12-Hydroxysydonic acid (5) | 282 | C15H22O5 | Marine sediment, Hsinchu, Taiwan | [54] |
| - | - | SP-1, marine sediment, Antarctic Great Wall Station | [40] | |
| - | - | SCSIO 41301, Phakellia fusca (marine sponge), Xisha Islands, China | [35] | |
| - | - | LW09, deep-sea sediment, Southwest Indian Ridge | [47] | |
| (7S,11S)-(+)-12-Acetoxysydonic acid (6) | 324 | C17H24O6 | ZSDS1-F6, unidentified marine sponge, Xisha Islands, China | [45] |
| (S)-(+)-Dehydrosydonic acid (7) | 264 | C15H20O4 | ZSDS1-F6, unidentified marine sponge, Xisha Islands, China | [45] |
| 7-Deoxy-7,14-didehydrosydonic acid (8) | 248 | C15H20O3 | CUGB-F126, seawater, Bohai Sea, Tianjin | [15] |
| - | - | SCSIO 41301, Phakellia fusca (marine sponge), Xisha Islands, China | [35] | |
| (E)-7-deoxy-7,8-didehydrosydonic acid (9) | 248 | C15H20O3 | SCSIO 41301, Phakellia fusca (marine sponge), Xisha Islands, China | [35] |
| (Z)-7-deoxy-7,8-didehydrosydonic acid (10) | 248 | C15H20O3 | SCSIO 41301, marine sponge Phakellia fusca, Xisha Islands, China | [35] |
| (−)-(R)-Cyclohydroxysydonic acid (11) | 280 | C15H20O5 | LW09, deep-sea sediment, Southwest Indian Ridge | [47] |
| Penicibisabolane G (12) | 264 | C15H20O4 | LW09, deep-sea sediment, Southwest Indian Ridge | [47] |
| 11,12-Dihydroxysydonic acid (13) | 298 | C15H22O6 | LW09, deep-sea sediment, Southwest Indian Ridge | [47] |
| Expansol G (14) | 324 | C17H24O6 | LW09, deep-sea sediment, Southwest Indian Ridge | [47] |
| Aspergillusene C (15) | 264 | C15H20O4 | ZSDS1-F6, unidentified marine sponge, Xisha Islands, China | [45] |
| Aspergillusene D (16) | 250 | C15H22O3 | SCSIO 41301, Phakellia fusca (marine sponge), Xisha Islands, China | [35] |
| Methyl (S)-(3-Hydroxy-4-(2-hydroxy-6-methylheptan-2-yl)benzoyl)glycinate = (+)-(7S)-Sydonic acid glycinate (17) | 337 | C18H27NO5 | CUGB-F126, seawater, Bohai Sea, Tianjin | [15] |
| Serine sydonate (18) | 353 | C18H27NO6 | Deep-sea mud, Dalian, China | [58] |
| - | - | Cultured, CPCC 401353, China | [59] | |
| 4′-Alkenyl serine sydonate (19) | 351 | C18H25NO6 | Deep-sea mud, Dalian, China | [58] |
| 4′-Hydroxyl serine sydonate (20) | 369 | C18H27NO7 | Deep-sea mud, Dalian, China | [58] |
| 5′-Hydroxyl serine sydonate (21) | 369 | C18H27NO7 | Deep-sea mud, Dalian, China | [58] |
| cyclo-12-Hydroxysydonic acid (22) | 264 | C15H20O4 | SCSIO 41301, Phakellia fusca (marine sponge), Xisha Islands, China | [35] |
| Sydowic acid (23) | 264 | C15H20O4 | Cultured, Japan | [27,29,30] |
| - | - | IFO 4284, cultured, Japan | [29,30] | |
| - | - | Acanthophora spicifera (red alga), Rameswaram, India | [53] | |
| - | - | CUGB-F126, seawater, Bohai Sea, Tianjin | [15] | |
| - | - | C1-S01-A7, seawater sample, West Pacific Ocean | [55] | |
| - | - | EN-434, Symphyocladia latiuscula (red alga), Qingdao coastline, China | [32] | |
| - | - | Rhododendron mole (leaves), Xing’an, Guangxi, China | [26] | |
| (7S,8S)-8-Hydroxysydowic acid (24) | 280 | C15H20O5 | EN-434, Symphyocladia latiuscula (red alga), Qingdao coastline, China | [32] |
| (±)-(7R*,10R*)-10-Hydroxysydowic acid (25) | 280 | C15H20O5 | EN-434, Symphyocladia latiuscula (red alga), Qingdao coastline, China | [32] |
| (−)-(7R,10S)-10-Hydroxysydowic acid (26) | 280 | C15H20O5 | MCCC 3A00324, deep-sea sediment, South Atlantic Ocean | [57] |
| - | - | Rhododendron mole (leaves), Xing’an, Guangxi, China | [26] | |
| (−)-(7R,10R)-iso-10-Hydroxysydowic acid (27) | 280 | C15H20O5 | MCCC 3A00324, deep-sea sediment, South Atlantic Ocean | [57] |
| Asperbisabolane A (28) | 278 | C15H18O5 | MCCC 3A00324, deep-sea sediment, South Atlantic Ocean | [57] |
| Asperbisabolane B (29) | 292 | C15H16O6 | MCCC 3A00324, deep-sea sediment, South Atlantic Ocean | [57] |
| Asperbisabolane C (30) | 280 | C15H20O5 | MCCC 3A00324, deep-sea sediment, South Atlantic Ocean | [57] |
| Asperbisabolane D (31) | 278 | C15H18O5 | MCCC 3A00324, deep-sea sediment, South Atlantic Ocean | [57] |
| Asperbisabolane E (32) | 280 | C15H20O5 | MCCC 3A00324, deep-sea sediment, South Atlantic Ocean | [57] |
| Asperbisabolane F (33) | 278 | C15H18O5 | MCCC 3A00324, deep-sea sediment, South Atlantic Ocean | [57] |
| Asperbisabolane G (34) | 280 | C15H20O5 | MCCC 3A00324, deep-sea sediment, South Atlantic Ocean | [57] |
| Asperbisabolane H (35) | 280 | C15H20O5 | MCCC 3A00324, deep-sea sediment, South Atlantic Ocean | [57] |
| Asperbisabolane I (36) | 280 | C15H20O5 | MCCC 3A00324, deep-sea sediment, South Atlantic Ocean | [57] |
| Asperbisabolane J (37) | 264 | C14H16O5 | MCCC 3A00324, deep-sea sediment, South Atlantic Ocean | [57] |
| Asperbisabolane K (38) | 284 | C13H16O5S | MCCC 3A00324, deep-sea sediment, South Atlantic Ocean | [57] |
| Asperbisabolane L (39) | 206 | C12H14O3 | MCCC 3A00324, deep-sea sediment, South Atlantic Ocean | [57] |
| Asperbisabolane M (40) | 280 | C15H20O5 | MCCC 3A00324, deep-sea sediment, South Atlantic Ocean | [57] |
| Asperbisabolane N (41) | 340 | C17H24O7 | MCCC 3A00324, deep-sea sediment, South Atlantic Ocean | [57] |
| Aspergillusene A = (E)-5-(Hydroxymethyl)-2-(6′-methylhept-2′-en-2′-yl)phenol (42) | 234 | C15H22O2 | PSU-F154, marine gorgonian sea fan of the genus Annella sp., coastal area, Surat Thani, Thailand | [56] |
| - | - | Marine sediment, Hsinchu, Taiwan | [54] | |
| - | - | ZSDS1-F6, unidentified marine sponge, Xisha Islands, China | [45] | |
| - | - | MCCC 3A00324, deep-sea sediment, South Atlantic Ocean | [57] | |
| - | - | LW09, deep-sea sediment, Southwest Indian Ridge | [47] | |
| Aspergillusene B (43) | 246 | C15H18O3 | PSU-F154, genus Annella sp. (gorgonian sea fan), coastal area, Surat Thani, Thailand | [56] |
| - | - | LW09, deep-sea sediment, Southwest Indian Ridge | [47] | |
| β-D-Glucopyranosyl aspergillusene A (44) | 396 | C21H32O7 | J05B-7F-4, Stelletta sp. (marine sponge), South Korea | [36] |
| (+)-(7S)-Sydonol (45) | 252 | C15H24O3 | MSX19583, spruce litter, Colorado, USA | [33] |
| - | - | Marine sediment, Hsinchu, Taiwan | [54] | |
| - | - | MCCC 3A00324, deep-sea sediment, South Atlantic Ocean | [57] | |
| (+)-(7S)-7-O-Methylsydonol (46) | 266 | C16H26O3 | Marine sediment, Hsinchu, Taiwan | [54] |
| 7-Deoxy-7,14-didehydrosydonol (47) | 234 | C15H22O2 | Marine sediment, Hsinchu, Taiwan | [54] |
| - | - | MCCC 3A00324, deep-sea sediment, South Atlantic Ocean | [57] | |
| (−)-5-(hydroxymethyl)-2-(2′,6′,6′-trimethyltetrahydro-2H-pyran-2-yl)phenol (48) | 250 | C15H22O3 | Rhododendron mole (leaves), Xing’an, Guangxi, China | [26] |
| Anhydrowaraterpol B (49) | 250 | C15H22O3 | Marine sediment, Hsinchu, Taiwan | [54] |
| - | - | ZSDS1-F6, unidentified marine sponge, Xisha Islands, China | [45] | |
| (Z)-5-(Hydroxymenthyl)-2-(6′)-methylhept-2′-en-2′-yl)-phenol (50) | 234 | C15H22O2 | ZSDS1-F6, unidentified marine sponge, Xisha Islands, China | [45] |
| - | - | MCCC 3A00324, deep-sea sediment, South Atlantic Ocean | [57] | |
| Methyl(R,E)-6-(2,3-dihydroxy-4-methylpenyl)-2-methylhept-5-enoate (51) | 278 | C16H22O4 | SW9, seawater sample, Yangma Island, Yantai, China | [41] |
| Cyclowaraterpol A (52) | 250 | C15H22O3 | ZSDS1-F6, unidentified marine sponge, Xisha Islands, China | [45] |
| (7S)-Flavilane A (53) | 298 | C16H26O3S | 10–31, deep-sea sediments, cold seep off southwestern Taiwan | [38] |
| (7S)-4-Iodo-flavilane A (54) | 424 | C16H25IO3S | 10–31, deep-sea sediments, cold seep off southwestern Taiwan | [38] |
| Aspersydosulfoxide A (55) | 280 | C16H24O2S | LW09, deep-sea sediment, Southwest Indian Ridge | [47] |
| Aspercuparene A (56) | 262 | C15H18O4 | MCCC 3A00324, deep-sea sediment, South Atlantic Ocean | [57] |
| Aspercuparene B (57) | 264 | C15H20O4 | MCCC 3A00324, deep-sea sediment, South Atlantic Ocean | [57] |
| Aspercuparene C (58) | 260 | C15H16O4 | MCCC 3A00324, deep-sea sediment, South Atlantic Ocean | [57] |
Table 2.
Mono- and triterpenoids and sterols reported from A. sydowii (molecular weight and formulae, strain, host, and location).
Table 2.
Mono- and triterpenoids and sterols reported from A. sydowii (molecular weight and formulae, strain, host, and location).
| Compound Name | Mol. Wt. | Mol. Formula | Strain, Host, Location | Ref. |
|---|---|---|---|---|
| Monoterpenoids | ||||
| Aspermonoterpenoid A (59) | 198 | C10H14O4 | MCCC 3A00324, deep-sea sediment, South Atlantic Ocean | [60] |
| Aspermonoterpenoid B (60) | 182 | C10H14O3 | MCCC 3A00324, deep-sea sediment, South Atlantic Ocean | [60] |
| Triterpenoids | ||||
| (4S,5S,6S,8S,9S,10R,13R,14S,16S,17Z)-6,16-Diacetoxy-25-hydroxy-3,7-dioxy-29-nordammara-1,17(20)-dien-21-oic acid (61) | 572 | C32H44O9 | PFW1-13, driftwood, beach of Baishamen, Hainan, China | [48] |
| Helvolic acid (62) | 554 | C32H42O8 | PFW1-13, driftwood, beach of Baishamen, Hainan, China | [48] |
| Sterols | ||||
| Ergosterol peroxide (63) | 430 | C28H46O3 | C1-S01-A7, seawater, West Pacific Ocean | [55] |
| Ergosta-7,22-dien-3β-ol (64) | 398 | C28H46O | C1-S01-A7, seawater, West Pacific Ocean | [55] |
| Ergosterol (65) | 396 | C28H44O | C1-S01-A7, seawater, West Pacific Ocean | [55] |
| β-Sitosterol (66) | 414 | C29H50O | C1-S01-A7, seawater, West Pacific Ocean | [55] |
| Cerevisterol (67) | 430 | C28H46O3 | YH11-2, deep-sea fungus, Guam, South Japan | [44] |
| (17R)-17-Methylincistererol (68) | 346 | C22H34O3 | YH11-2, deep-sea fungus, Guam, South Japan | [44] |
Table 3.
Xanthones and quinones reported from Aspergillus sydowii (molecular weight and formulae, strain, host, and location).
Table 3.
Xanthones and quinones reported from Aspergillus sydowii (molecular weight and formulae, strain, host, and location).
| Compound Name/Chemical Class | Mol. Wt. | Mol. Formula | Strain, Host, and Location | Ref. |
|---|---|---|---|---|
| Xanthones | ||||
| Sydowinin A (69) | 300 | C16H12O6 | Cultured, IFO 4284, Japan | [29] |
| - | - | PSU-F154, genus Annella sp. (gorgonian sea fan), coastal area, Surat Thani, Thailand | [56] | |
| 12-O-Acetyl-sydowinin A (70) | 342 | C18H14O7 | C1-S01-A7, seawater, West Pacific Ocean | [55] |
| Sydowinin B (71) | 316 | C16H12O7 | Cultured, IFO 4284, Japan | [29] |
| - | - | Marine sediment, Hsinchu, Taiwan | [54] | |
| - | - | PSU-F154, genus Annella sp. (gorgonian sea fan), coastal area, Surat Thani, Thailand | [56] | |
| - | - | Marine sediment, Hsinchu, Taiwan | [54] | |
| - | - | C1-S01-A7, seawater, West Pacific Ocean | [55] | |
| 13-O-Acetylsydowinin B (72) | 358 | C18H14O8 | Scapania ciliata (Chinese liverwort), Maoer Mountain, Guangxi, China | [63] |
| - | - | J05B-7F-4, Stelletta sp. (marine sponge), South Korea | [36] | |
| - | - | C1-S01-A7, seawater, West Pacific Ocean | [55] | |
| Methyl 8-hydroxy-6-methyl-9-oxo-9H-xanthene-1-carboxylate (73) | 284 | C16H12O5 | PSU-F154, genus Annella sp. (gorgonian sea fan), coastal area, Surat Thani, Thailand | [56] |
| Pinselin (74) | 300 | C16H12O6 | PSU-F154, genus Annella sp. (gorgonian sea fan), coastal area, Surat Thani, Thailand | [56] |
| - | - | Scapania ciliata (Chinese liverwort), Maoer Mountain, Guangxi, China | [63] | |
| - | - | C1-S01-A7, seawater, West Pacific Ocean | [55] | |
| Methyl 1,6-dihydroxy-3-methyl-9-oxo-9H-xanthene-1-carboxylate (75) | 300 | C16H12O6 | Scapania ciliata (Chinese liverwort), Maoer Mountain, Guangxi, China | [56] |
| Sydoxanthone A (76) | 388 | C19H16O7S | Scapania ciliata (Chinese liverwort), Maoer Mountain, Guangxi, China | [63] |
| Sydoxanthone B (77) | 346 | C17H14O6S | Scapania ciliata (Chinese liverwort), Maoer Mountain, Guangxi, China | [63] |
| 8-Hydroxy-6-methyl-9-oxo-9H-xanthene-1-carboxylic acid methyl ester (78) | 284 | C16H12O5 | Scapania ciliata (Chinese liverwort), Maoer Mountain, Guangxi, China | [63] |
| 2-Hydroxy-6-formyl-vertixanthone (79) | 314 | C16H10O7 | C1-S01-A7, seawater, West Pacific Ocean | [55] |
| 2-Hydroxy-1-(hydroxymethyl)-8-methoxy-3-methyl-9H-xanthen-9-one (80) | 286 | C16H14O5 | SCSIO 41301, Phakellia fusca (marine sponge), Xisha Islands, China | [35] |
| 2-Hydroxy-1-(hydroxymethyl)-7,8-dimethoxy-3-methyl-9H-xanthen-9-one (81) | 316 | C17H16O6 | SCSIO 41301, Phakellia fusca (marine sponge), Xisha Islands, China | [35] |
| Austocystin A (82) | 372 | C19H13ClO6 | SCSIO 00305, Verrucella unbracculum (gorgonian), South China Sea, Sanya, Hainan, China | [24] |
| 6-Methoxyl austocystin A (83) | 402 | C20H15ClO7 | SCSIO 00305, Verrucella unbracculum (gorgonian), South China Sea, Sanya, Hainan, China | [24] |
| Sterigmatocystin (84) | 324 | C18H12O6 | DC08, Dachtylospongia sp. (marine sponge), South Coast, West Sumatra, Indonesia | [39] |
| Sydowinol (85) | 318 | C16H14O7 | IFO 4284, Cultured, Japan | [29] |
| Aspergillusone A (86) | 304 | C16H16O6 | PSU-F154, genus Annella sp. (gorgonian sea fan), coastal area, Surat Thani, Thailand | [56] |
| - | - | C1-S01-A7, seawater, West Pacific Ocean | [55] | |
| Aspergillusone B (87) | 338 | C16H18O8 | PSU-F154, genus Annella sp. (gorgonian sea fan), coastal area, Surat Thani, Thailand | [56] |
| (7R,8R)-AGI-B4 (88) | 320 | C16H16O7 | PSU-F154, genus Annella sp. (gorgonian sea fan), coastal area, Surat Thani, Thailand | [56] |
| - | - | Marine sediment, Hsinchu, Taiwan | [54] | |
| - | - | C1-S01-A7, seawater, West Pacific Ocean | [55] | |
| 12-O-Acetyl (7R,8R)-AGI-B4 (89) | 362 | C18H18O8 | C1-S01-A7, seawater, West Pacific Ocean | [55] |
| (7R,8R)-α-Diversonolic ester (90) | 322 | C16H18O7 | PSU-F154, genus Annella sp. (gorgonian sea fan), coastal area, Surat Thani, Thailand | [56] |
| Quinones | ||||
| Emodin (91) | 270 | C15H10O5 | Scapania ciliata (Chinese liverwort), Maoer Mountain, Guangxi, China | [63] |
| - | - | C1-S01-A7, seawater, West Pacific Ocean | [55] | |
| Emodic acid (92) | 300 | C15H8O7 | SCSIO 41301, Phakellia fusca (marine sponge), Xisha Islands, China | [35] |
| Parietinic acid (93) | 314 | C16H10O7 | SCSIO 41301, Phakellia fusca (marine sponge), Xisha Islands, China | [35] |
| Questin (94) | 284 | C16H12O5 | Scapania ciliata (Chinese liverwort), Maoer Mountain, Guangxi, China | [63] |
| - | - | C1-S01-A7, seawater, West Pacific Ocean | [55] | |
| - | - | SCSIO 41301, marine sponge Phakellia fusca, Xisha Islands, China | [35] | |
| 1,6,8-Trihydroxy-3-methylanthraquinone (95) | 270 | C15H10O5 | SCSIO 41301, marine sponge Phakellia fusca, Xisha Islands, China | [35] |
| Yicathin C (96) | 312 | C17H12O6 | C1-S01-A7, seawater sample, West Pacific Ocean | [55] |
| 1-Hydroxy-6,8-dimethoxy-3-methylanthraquinone (97) | 298 | C17H14O5 | Scapania ciliata (Chinese liverwort), Maoer Mountain, Guangxi, China | [63] |
| (+)-3,3′,7,7′,8,8′-hexahydroxy-5,5′-dimethyl-bianthra-quinone (98) | 538 | C30H18O10 | #2B, leaves, Aricennia marina, Yangjiang, Guangdong, China | [64] |
| Xanthoradone A (99) | 490 | C27H22O9 | #2B, leaves, Aricennia marina, Yangjiang, Guangdong, China | [64] |
Table 4.
Alkaloids reported from Aspergillus sydowii (molecular weight and formulae, strain, host, and location).
Table 4.
Alkaloids reported from Aspergillus sydowii (molecular weight and formulae, strain, host, and location).
| Compound Name | Mol. Wt. | Mol. Formula | Strain, Host, and Location | Ref. |
|---|---|---|---|---|
| Cyclotryprostatin B (100) | 425 | C23H27N3O5 | SCSIO 00305, Verrucella umbraculum (gorgonian), Sanya, Hainan, China | [31] |
| Cyclotryprostatin E (101) | 443 | C23H29N3O6 | SCSIO 00305, Verrucella umbraculum (gorgonian), Sanya, Hainan, China | [31] |
| Fumitremorgin B (102) | 479 | C27H33N3O5 | SCSIO 00305, Verrucella umbraculum (gorgonian), Sanya, Hainan, China | [31] |
| 6-Methoxyspirotryprostatin B (103) | 393 | C22H23N3O4 | PFW1-13, driftwood, Baishamen beach, Hainan, China | [48] |
| 18-Oxotryprostatin A (104) | 395 | C22H25N3O4 | PFW1-13, driftwood, Baishamen beach, Hainan, China | [48] |
| 14-Hydroxyterezine D (105) | 341 | C19H23N3O3 | PFW1-13, driftwood, Baishamen beach, Hainan, China | [48] |
| Spirotryprostatin A (106) | 365 | C21H23N3O2 | PFW1-13, driftwood, Baishamen beach, Hainan, China | [48] |
| Terezine D (107) | 325 | C19H23N3O2 | PFW1-13, driftwood, Baishamen beach, Hainan, China | [48] |
| Fumitremorgin C (108) | 379 | C22H25N3O3 | PFW1-13, driftwood, Baishamen beach, Hainan, China | [48] |
| 12,13-Dihydroxyfumitremorgin C (109) | 411 | C22H25N3O5 | PFW1-13, driftwood, Baishamen beach, Hainan, China | [48] |
| (11S,14S)-Cyclo-(L-Trp-L-Phe) (110) | 333 | C20H19N3O2 | PSU-F154, genus Annella sp. (gorgonian sea fan), coastal area, Surat Thani, Thailand | [56] |
| - | - | MSX19583, spruce litter, Colorado, USA | [33] | |
| - | - | J05B-7F-4, Stelletta sp. (marine sponge), South Korea | [36] | |
| - | - | ZSDS1-F6, unidentified marine sponge, Xisha Islands, China | [45] | |
| - | - | SP-1, marine sediment, Antarctic Great Wall Station | [40] | |
| - | - | MCCC 3A00324, deep-sea sediment, South Atlantic Ocean | [65] | |
| Didehydrobisdethiobis(methylthio)gliotoxin (111) | 356 | C15H20N2O4S2 | PFW1-13, driftwood, Baishamen beach, Hainan, China | [48] |
| Verruculogen (112) | 354 | C15H18N2O4S2 | PFW1-13, driftwood, Baishamen beach, Hainan, China | [48] |
| Cyclo-(S-Pro-S-Ile) (114) | 210 | C11H18N2O2 | Cultured, China | [28] |
| Cyclo-(S-Pro-R-Leu) (113) | 210 | C11H18N2O2 | Cultured, China | [28] |
| WIN 64821 (115) | 664 | C40H36N6O4 | MSX19583, spruce litter, Colorado, USA | [33] |
| - | - | C1-S01-A7, seawater, West Pacific Ocean | [55] | |
| Bisdethiobis(methylthio)-acetylaranotin (116) | 534 | C24H26N2O8S2 | Cultured, China | [28] |
| [4-(2-Methoxyphenyl)-1-piperazinyl][(1-methyl-1H-indol-3-yl)]-methanone (117) | 349 | C21H23N3O2 | SCSIO 00305, Verrucella umbraculum (gorgonian), Sanya, Hainan, China | [31] |
| Fumiquinazoline A (118) | 445 | C24H23N5O4 | SCSIO 00305, Verrucella umbraculum (gorgonian), Sanya, Hainan, China | [31] |
| Fumiquinazoline B (119) | 445 | C24H23N5O4 | SCSIO 00305, Verrucella umbraculum (gorgonian), Sanya, Hainan, China | [31] |
| Fumiquinazoline C (120) | 443 | C24H21N5O4 | SCSIO 00305, Verrucella umbraculum (gorgonian), Sanya, Hainan, China | [31] |
| Fumiquinazoline D (121) | 443 | C24H21N5O4 | SCSIO 00305, Verrucella umbraculum (gorgonian), Sanya, Hainan, China | [31] |
| Fumiquinazoline F (122) | 358 | C21H18N4O2 | SCSIO 00305, Verrucella umbraculum (gorgonian), Sanya, Hainan, China | [31] |
| Fumiquinazoline G (123) | 358 | C21H18N4O2 | SCSIO 00305, Verrucella umbraculum (gorgonian), Sanya, Hainan, China | [31] |
| 2-(4-Hydroxybenzyl)-4-(3-acetyl)quinazolin-one (124) | 294 | C17H14N2O3 | SW9, seawater, Yangma Island, Yantai, China | [41] |
| 2-(4-Hydroxybenzoyl)-4(3H)-quinazolinone (125) | 252 | C15H12N2O2 | SW9, seawater, Yangma Island, Yantai, China | [41] |
| 2-(4-Oxo-3,4-dihydroquinazolin-2-yl)benzoic acid (126) | 266 | C15H10N2O3 | MCCC 3A00324, deep-sea sediment, South Atlantic Ocean | [65] |
| Acremolin (127) | 231 | C11H13N5O | MCCC 3A00324, deep-sea sediment, South Atlantic Ocean | [65] |
| Acremolin C (128) | 245 | C12H15N5O | SP-1, marine sediment, Antarctic Great Wall Station | [40] |
| Acremolin D (129) | 289 | C13H15N5O3 | MCCC 3A00324, deep-sea sediment, South Atlantic Ocean | [65] |
| Pseustin A (130) | 431 | C22H25NO8 | PFW1-13, driftwood, Baishamen beach, Hainan, China | [48] |
| 14-Norpseurotin A (131) | 417 | C21H23NO8 | PFW1-13, driftwood, Baishamen beach, Hainan, China | [48] |
| Azaspirofurans A (132) | 411 | C21H19NO7 | D2-6, Marine sediment, Jiaozhou Bay, China | [43] |
| Azaspirofurans B (133) | C22H21NO7 | D2-6, Marine sediment, Jiaozhou Bay, China | [43] | |
| Chrysotriazole A (134) | 311 | C17H17N3O3 | SW9, seawater, Yangma Island, Yantai, China | [41] |
| Indoleacetic acid (135) | 175 | C10H9NO2 | MCCC 3A00324, deep-sea sediment, South Atlantic Ocean | [65] |
| Pyrrole-2-carboxylic acid (136) | 111 | C5H5NO2 | MCCC 3A00324, deep-sea sediment, South Atlantic Ocean | [65] |
| 2-Acetylaminobenzamide (137) | 178 | C9H10N2O2 | C1-S01-A7, seawater, West Pacific Ocean | [55] |
| 1,4-Dioxa-9,12-diazacyclohexadecane-5,8,13,16-tetraone (138) | 286 | C12H18N2O6 | Cultured, China | [28] |
| N-Acetyltyramine (139) | 179 | C10H13NO2 | Cultured, China | [28] |
| Fumigaclavine B (140) | 366 | C23H30N2O2 | PFW1-13, driftwood, Baishamen beach, Hainan, China | [48] |
| Fumigaclavine C (141) | 298 | C18H22N2O2 | PFW1-13, driftwood, Baishamen beach, Hainan, China | [48] |
| Pyripyropene A (142) | 525 | C29H35NO8 | PFW1-13, driftwood, Baishamen beach, Hainan, China | [48] |
| Pyripyropene E (143) | 569 | C30H35NO10 | PFW1-13, driftwood, Baishamen beach, Hainan, China | [48] |
Table 5.
Phenyl ether derivatives reported from Aspergillus sydowii (molecular weight and formulae, strain, host, and location).
Table 5.
Phenyl ether derivatives reported from Aspergillus sydowii (molecular weight and formulae, strain, host, and location).
| Compound Name | Mol. Wt. | Mol. Formula | Strain, Host, Location | Ref. |
|---|---|---|---|---|
| Violaceol I (144) | 262 | C14H14O5 | MF357, sea sediment, East China Sea, China | [37] |
| - | - | J05B-7F-4, Stelletta sp. (marine sponge), South Korea | [36] | |
| Violaceol II (145) | 248 | C13H12O5 | MF357, sea sediment, East China Sea, China | [37] |
| - | - | J05B-7F-4, Stelletta sp. (marine sponge), South Korea | [36] | |
| Diorcinol (146) | 230 | C14H14O3 | Marine sediment, Hsinchu, Taiwan | [54] |
| - | - | J05B-7F-4, Stelletta sp. (marine sponge), South Korea | [36] | |
| - | - | FNA026, seawater, Xiamen, China | [9] | |
| - | - | MCCC 3A00324, deep-sea sediment, South Atlantic Ocean | [60] | |
| 4-Carboxydiorcinal (147) | 274 | C15H14O5 | J05B-7F-4, Stelletta sp. (marine sponge), South Korea | [36] |
| FNA026, seawater, Xiamen, China | [9] | |||
| Diorcinolic acid (148) | 318 | C16H14O7 | J05B-7F-4, Stelletta sp. (marine sponge), South Korea | [36] |
| Glyceryl diorcinolic acid (149) | 392 | C19H20O9 | FNA026, seawater, Xiamen, China | [9] |
| 4-Methoxycarbonyl diorcinol (150) | 288 | C16H16O5 | FNA026, seawater, Xiamen, China | [9] |
| 10-Deoxygerfelin (151) | 274 | C15H14O5 | CPCC 401353, cultured, China | [59] |
| Cordyol C (152) | 246 | C14H14O4 | J05B-7F-4, Stelletta sp. (marine sponge), South Korea | [36] |
| - | - | FNA026, seawater, Xiamen, China | [9] | |
| - | - | MCCC 3A00324, deep-sea sediment, South Atlantic Ocean | [60] | |
| Cordyol E (153) | 244 | C15H16O3 | J05B-7F-4, Stelletta sp. (marine sponge), South Korea | [36] |
| Cordyol F (154) | 276 | C15H16O5 | FNA026, seawater, Xiamen, China | [9] |
| Cordyol C-3-O-α-D-ribofuranoside (155) | 378 | C19H22O8 | FNA026, seawater, Xiamen, China | [9] |
| Diorcinol-3-O-α-D-ribofuranoside (156) | 362 | C19H22O7 | FNA026, seawater, Xiamen, China | [9] |
| 4-Methoxycarbonyl diorcinol-3-O-α-D-glucoside (157) | 450 | C22H26O10 | FNA026, seawater, Xiamen, China | [9] |
| Disydonol B (158) | 486 | C30H46O5 | FNA026, seawater, Xiamen, China | [55] |
| 2-(Ethoxycarbonyl)-4′-carboxydiorcinal (159) | 348 | C17H16O8 | FNA026, seawater, Xiamen, China | [9] |
| 7-Ethyldiorcinol (160) | 244 | C15H16O3 | FNA026, seawater, Xiamen, China | [9] |
| 3-Hydroxydiorcinol (161) | 246 | C14H14O4 | FNA026, seawater, Xiamen, China | [9] |
| Aspergilol E (162) | 304 | C16H16O6 | FNA026, seawater, Xiamen, China | [9] |
| 4-Hydroxy-2-(3′-hydroxy-4-methoxycarbonyl-5′-methylphenoxy)-6-methylbenzoic acid (163) | 332 | C17H16O7 | FNA026, seawater, Xiamen, China | [9] |
| Aspermutarubrol (164) | 262 | C14H14O5 | FNA026, seawater, Xiamen, China | [9] |
| Bisviolaceol II (165) | 506 | C28H26O9 | 10–31, sediments, deep-sea, cold seep off southwestern Taiwan | [38] |
| Sydowiol A (166) | 370 | C20H18O7 | MF357, sea sediment, East China Sea, China | [37] |
| Sydowiol B (167) | 384 | C21H20O7 | MF357, sea sediment, East China Sea, China | [37] |
| Sydowiol C (168) | 384 | C21H20O7 | MF357, sea sediment, East China Sea, China | [37] |
Table 6.
Chromane and coumarin derivatives reported from Aspergillus sydowii (molecular weight and formulae, strain, host, and location).
Table 6.
Chromane and coumarin derivatives reported from Aspergillus sydowii (molecular weight and formulae, strain, host, and location).
| Compound Name | Mol. Wt. | Mol. Formula | Strain, Host, Location | Ref. |
|---|---|---|---|---|
| Citrinin (169) | 250 | C13H14O5 | EN-534, Laurencia okamurai (red alga), Qingdao, China | [69] |
| Penicitrinol A (170) | 382 | C23H26O5 | EN-534, Laurencia okamurai (red alga), Qingdao, China | [[6] |
| seco-Penicitrinol A (171) | 398 | C23H26O6 | EN-534, Laurencia okamurai (red alga), Qingdao, China | [69] |
| Penicitrinol L (172) | 266 | C14H18O5 | EN-534, Laurencia okamurai (red alga), Qingdao, China | [69] |
| Penicitrinone A (173) | 380 | C23H24O5 | EN-534, Laurencia okamurai (red alga), Qingdao, China | [69] |
| Penicitrinone F (174) | 394 | C24H26O5 | EN-534, Laurencia okamurai (red alga), Qingdao, China | [69] |
| Dihydrocitrinone (175) | 266 | C13H14O6 | EN-534, Laurencia okamurai (red alga), Qingdao, China | [69] |
| Decarboxydihydrocitrinone (176) | 222 | C12H14O4 | EN-534, Laurencia okamurai (red alga), Qingdao, China | [69] |
| (−)-Asperentin (177) | 292 | C16H20O5 | F00785, Enteromorpha prolifera (green alga), Jinjiang Saltern, Fujian province, China | [70] |
| LF660, sea sediment, Mediterranean Sea, Levantine Basin SE of Crete | [46] | |||
| Asperentin B (178) | 308 | C16H20O6 | LF660, sea sediment, Mediterranean Sea, Levantine Basin SE of Crete | [46] |
| 5-O-Methyl-asperentin B = 5-Hydroxyl-6-O-methylasperentin (179) | 322 | C17H22O6 | F00785, Enteromorpha prolifera (green alga), Jinjiang Saltern, Fujian province, China | [70] |
| LF660, sea sediment, Mediterranean Sea, Levantine Basin SE of Crete | [46] | |||
| 6-O-α-D-Ribosylasperentin (180) | 424 | C21H28O9 | F00785, Enteromorpha prolifera (green alga), Jinjiang Saltern, Fujian province, China | [70] |
| 6-O-α-D-Ribosyl-8-O-methylasperentin (181) | 438 | C22H30O9 | F00785, Enteromorpha prolifera (green alga), Jinjiang Saltern, Fujian province, China | [70] |
| 5′-Hydroxyasperentin (182) | 308 | C16H20O6 | F00785, Enteromorpha prolifera (green alga), Jinjiang Saltern, Fujian province, China | [70] |
| 4′-Hydroxyasperentin (183) | 308 | C16H20O6 | F00785, Enteromorpha prolifera (green alga), Jinjiang Saltern, Fujian province, China | [70] |
| Asperentin-8-methyl ether (184) | 306 | C17H22O5 | F00785, Enteromorpha prolifera (green alga), Jinjiang Saltern, Fujian province, China | [70] |
| 5′-Hydroxyasperentin-8-methyl ether (185) | 322 | C17H22O6 | F00785, Enteromorpha prolifera (green alga), Jinjiang Saltern, Fujian province, China | [70] |
| 4′-Hydroxyasperentin-6-methyl ether (186) | 322 | C17H22O6 | F00785, Enteromorpha prolifera (green alga), Jinjiang Saltern, Fujian province, China | [70] |
| (3R,4S)-3,4,5-Trimethyl-isochroman-6,8-diol (187) | 208 | C12H16O3 | YH11-2, deep-sea fungus, Guam, South Japan | [44] |
| (3R,4S)-6,8-dihydroxy-3,4,5-trimethylisochroman-1-one (188) | 222 | C12H14O4 | YH11-2, deep-sea fungus, Guam, South Japan | [44] |
| 2-(12S-Hydroxypropyl)-3-hydroxymethyl-6-hydroxy-7-methoxychromone (189) | 280 | C14H16O6 | #2B, Aricennia marina (leaves), Yangjiang, Guangdong, China | [64] |
| 7-Hydroxy-2-(2-hydroxypropyl)-5-methyl chromone (190) | 234 | C13H14O4 | J05B-7F-4, Stelletta sp. (marine sponge), South Korea | [36] |
| Aspercoumarine acid (191) | 206 | C10H6O5 | MCCC 3A00324, deep-sea sediment, South Atlantic Ocean | [60] |
| (2R)-2,3-Dihydro-7-hydroxy-6, 8-dimethyl-2-[(E)-prop-1-enyl]chromen-4-one (192) | 232 | C14H16O3 | YH11-2, deep-sea fungus, Guam, South Japan | [44] |
Table 7.
Chromane and coumarin derivatives reported from Aspergillus sydowii (molecular weight and formulae, strain, host, and location).
Table 7.
Chromane and coumarin derivatives reported from Aspergillus sydowii (molecular weight and formulae, strain, host, and location).
| Compound Name | Mol. Wt. | Mol. Formula | Strain, Host, Location | Ref. |
|---|---|---|---|---|
| 4-Hydroxy-3,6-dimethyl-2-pyrone (194) | 140 | C7H8O3 | SCSIO 41301, Phakellia fusca (marine sponge), Xisha Islands, China | [35] |
| 4-Methyl-5,6-dihydropyren-2-one (193) | 112 | C6H8O2 | SCSIO 41301, Phakellia fusca (marine sponge), Xisha Islands, China | [35] |
| Sydowione A (195) | 226 | C12H18O4 | SCSIO 00305, Verrucella unbracculum (gorgonian), South China Sea, Sanya, Hainan, China | [24] |
| Sydowione B (196) | 226 | C12H18O4 | SCSIO 00305, Verrucella unbracculum (gorgonian), South China Sea, Sanya, Hainan, China | [24] |
| Paecilpyrone A (197) | 238 | C13H18O4 | SCSIO 00305, Verrucella unbracculum (gorgonian), South China Sea, Sanya, Hainan, China | [24] |
| (±)-Pyrenocine S (198) | 226 | C11H14O5 | #2B, Aricennia marina (leaves), Yangjiang, Guangdong, China | [64] |
| Pyrenocine A (199) | 208 | C11H12O4 | #2B, Aricennia marina (leaves), Yangjiang, Guangdong, China | [64] |
| (±)-Pyrenocine E (200) | 240 | C12H16O5 | #2B, Aricennia marina (leaves), Yangjiang, Guangdong, China | [64] |
| Asperphenylpyrone (201) | 310 | C18H14O5 | MCCC 3A00324, deep-sea sediment, South Atlantic Ocean | [60] |
| Macrolactin U′ (202) | 480 | C31H44O4 | Deep-sea mud, Dalian, China | [58] |
| Sydocyclopropane A (203) | 270 | C14H22O5 | MCCC 3A00324, deep-sea sediment, South Atlantic Ocean | [42] |
| Sydocyclopropane B (204) | 182 | C11H18O2 | MCCC 3A00324, deep-sea sediment, South Atlantic Ocean | [42] |
| Sydocyclopropane C (205) | 184 | C10H16O3 | MCCC 3A00324, deep-sea sediment, South Atlantic Ocean | [42] |
| Sydocyclopropane D (206) | 184 | C10H16O3 | MCCC 3A00324, deep-sea sediment, South Atlantic Ocean | [42] |
| Hamavellone B (207) | 180 | C11H16O2 | MCCC 3A00324, deep-sea sediment, South Atlantic Ocean | [42] |
| Sydowione C (208) | 284 | C15H24O5 | SCSIO 00305, Verrucella unbracculum (gorgonian), South China Sea, Sanya, Hainan, China | [24] |
| Cycloerodiol (209) | 240 | C15H28O2 | Cultured, China | [28] |
| Sydowin A (210) | 412 | C18H14Cl2O7 | Acanthophora spicifera (red alga), Rameswaram, India | [53] |
| Sydowin B (211) | 396 | C18H14Cl2O6 | Acanthophora spicifera (red alga), Rameswaram, India | [53] |
| 3-(2-Hydroxypropyl)-4-(hexa-2E,4E-dien-6-yl)furan-2(5H)-one (212) | 222 | C13H18O3 | Cultured, China | [28] |
| Pestalotiolactone A (213) | 184 | C10H16O3 | MCCC 3A00324, deep-sea sediment, South Atlantic Ocean | [60] |
| 1-Hydroxyboivinianin A (214) | 206 | C12H14O3 | MCCC 3A00324, deep-sea sediment, South Atlantic Ocean | [57] |
| (±)-Sydowiccal (215) | 222 | C12H14O4 | Rhododendron mole (leaves), Xing’an, Guangxi, China | [26] |
| Butyrolactone-I (216) | 424 | C24H24O7 | #2B, Aricennia marina (leaves), Yangjiang, Guangdong, China | [64] |
Table 8.
Other metabolites reported from Aspergillus sydowii (molecular weight and formulae, strain, host, and location).
Table 8.
Other metabolites reported from Aspergillus sydowii (molecular weight and formulae, strain, host, and location).
| Compound Name | Mol. Wt. | Mol. Formula | Strain, Host, Location | Ref. |
|---|---|---|---|---|
| Sydowether (217) | 354 | C18H26O7 | SW9, seawater, Yangma Island, Yantai, China | [41] |
| 1,9-Dihydroxy-3-(hydroxymethyl)-10-methoxydibenzo[b,e]oxepine- 6,11-dione (218) | 316 | C16H12O7 | Scapania ciliata (Chinese liverwort), Maoer Mountain, Guangxi, China | [63] |
| 8-Demethoxy-10-methoxy-wentiquinone C (219) | 300 | C16H12O6 | C1-S01-A7, seawater, West Pacific Ocean | [55] |
| Moniliphenone (220) | 286 | C16H14O5 | Scapania ciliata (Chinese liverwort), Maoer Mountain, Guangxi, China | [63] |
| Phenol A acid (221) | 240 | C12H16O5 | EN-534, Laurencia okamurai (red alga), Qingdao, China | [69] |
| Phenol A (222) | 196 | C11H16O3 | EN-534, Laurencia okamurai (red alga), Qingdao, China | [69] |
| 3-(2,5-Dimethylbenzo[d][1,3]dioxol-2-yl)propanoic acid (223) | 222 | C12H14O4 | SCSIO 41301, Phakellia fusca (marine sponge), Xisha Islands, China | [35] |
| 2-(5-Hydroxy-4-methylpentyl)-2-methylbenzo[d][1,3]dioxole-5- carboxylic acid (224) | 280 | C15H20O5 | SCSIO 41301, Phakellia fusca (marine sponge), Xisha Islands, China | [35] |
| 4-Hydroxyphenylacetic acid (225) | 152 | C8H8O3 | SP-1, marine sediment, Antarctic Great Wall Station | [40] |
| Orcinol (226) | 124 | C7H8O2 | PSU-F154, genus Annella sp. (gorgonian sea fan), coastal area, Surat Thani, Thailand | [56] |
| 3-Hydroxybenzoic acid (227) | 138 | C7H6O3 | CPCC 401353, cultured, China | [59] |
| 4-Hydroxybenzoic acid (228) | 138 | C7H6O3 | MCCC 3A00324, deep-sea sediment, South Atlantic Ocean | [60] |
| 3,4,5-Trimethoxybenzoic acid (229) | 212 | C10H12O5 | MCCC 3A00324, deep-sea sediment, South Atlantic Ocean | [60] |
| 4-(3′,4′-Dihydroxyphenyl)-2-butanone (230) | 180 | C10H12O3 | MCCC 3A00324, deep-sea sediment, South Atlantic Ocean | [60] |
| 4-Hydroxybenzaldehyde (231) | 122 | C7H6O2 | C1-S01-A7, seawater, West Pacific Ocean | [55] |
| Benzoic acid (232) | 122 | C7H6O2 | CPCC 401353, cultured, China | [59] |
| Gibellulin B (233) | 260 | C14H12O5 | FNA026, seawater, Xiamen, China | [9] |
| 3,7-Dihydroxy-1,9-dimethyldibenzofuran (234) | 228 | C14H12O3 | FNA026, seawater, Xiamen, China | [9] |
| - | - | SCSIO 41301, Phakellia fusca (marine sponge), Xisha Islands, China | [35] | |
| - | - | MCCC 3A00324, deep-sea sediment, South Atlantic Ocean | [60] | |
| Orsellinic acid (235) | 168 | C8H8O4 | Deep-sea mud, Dalian, China | [58] |
| - | - | CPCC 401353, cultured, China | [59] | |
| 2-Methoxy-5-methyl-3-(methylsulfonyl)phenol (236) | 216 | C9H12O4S | Rhododendron mole (leaves), Xing’an, Guangxi, China | [26] |
| 2,3,5-Trimethyl-6-(3-oxobutan-2-yl)-4H-pyran-4-one (237) | 208 | C12H16O3 | YH11-2, deep-sea fungus, Guam, South Japan | [44] |
| 5-[(2S,3R)-3-Hydroxybutan-2-yl]-4-methylbenzene-1,3-diol (238) | 196 | C11H16O3 | YH11-2, deep-sea fungus, Guam, South Japan | [44] |
| 2,4-Dihydroxy-3,5,6-trimethylbenzaldehyde (239) | 180 | C10H12O3 | YH11-2, deep-sea fungus, Guam, South Japan | [44] |
| Macrolactin A (240) | 402 | C24H34O5 | Piece of deep-sea mud, Dalian, China | [58] |
| (Z)-6-Tridecenoic acid (241) | 212 | C13H24O2 | Cultured, China | [28] |
| Malvidin 3-O-glucoside (242) | 479 | C22H23O12+\ | H-1, bacterial wilt-affected ginger humus, Chengdu, China | [25] |
| Malvidin 3-O-galactoside (243) | 449 | C21H21O11+ | H-1, bacterial wilt-affected ginger humus, Chengdu, China | [25] |
| Cyanidin 3-O-glucoside (244) | 493 | C23H25O12+ | H-1, bacterial wilt-affected ginger humus, Chengdu, China | [25] |
| Peonidin O-malonylhexoside (245) | 549 | C25H25O14+ | H-1, bacterial wilt-affected ginger humus, Chengdu, China | [25] |
| Cyanidin (246) | 287 | C15H11O6+ | H-1, bacterial wilt-affected ginger humus, Chengdu, China | [25] |
Table 9.
Cytotoxic metabolites reported from A. sydowii.
| Compound Name | Assay/Cell Line | Biological Results (IC50) * | Ref. | |
|---|---|---|---|---|
| Compound | Positive Control | |||
| Cerevisterol (67) | P388/SRB | 0.12 μM | CDDP 0.039 μM | [44] |
| 6-Methoxyl austocystin A (83) | Artemia salina | 2.9 µM | Toosendanin 2.2 µM | [24] |
| [4-(2-Methoxyphenyl)-1-piperazinyl][(1-methyl-1H-indol-3-yl)]-methanone (117) | MTT/A375 | 5.7 μM | - | [31] |
| (3R,4S)-3,4,5-Trimethylisochroman-6,8-diol (187) | P388/SRB | 1.95 μM | CDDP 0.039 μM | [44] |
| (2R)-2,3-Dihydro-7-hydroxy-6,8-dimethyl-2-[(E)-prop-1-enyl] chromen-4-one (192) | P388/SRB | 0.14 μM | CDDP 0.039 μM | [44] |
| Sydowione A (195) | Artemia salina | 19.5 µM | Toosendanin 2.2 µM | [24] |
| Sydowione B (196) | Artemia salina | 14.3 µM | Toosendanin 2.2 µM | [24] |
| Sydowione C (208) | Artemia salina | 8.3 µM | Toosendanin 2.2 µM | [24] |
| 2,4-Dihydroxy-3,5,6-trimethylbenzaldehyde (239) | P388/SRB | 0.59 μM | CDDP 0.039 μM | [44] |
* IC50, Half maximal inhibitory concentration.
Table 10.
Anti-mycobacterial, antimicrobial, and anti-microalgal metabolites reported from A. sydowii.
Table 10.
Anti-mycobacterial, antimicrobial, and anti-microalgal metabolites reported from A. sydowii.
| Compound Name | Assay/Organism | Biological Results | Ref. | |
|---|---|---|---|---|
| Compound | Positive Control | |||
| Antibacterial (MIC) | ||||
| (7S)-(+)-hydroxysydonic acid (2) | Broth microdilution/S. aureus | 0.5 µg/mL | Tigecycline 0.06 µg/mL | [40] |
| Broth microdilution/ MRSA | 1 µg/mL | Tigecycline 0.25 µg/mL | [40] | |
| Broth microdilution/S. epidermidis | 0.25 µg/mL | Tigecycline 0.03 µg/mL | [40] | |
| Broth microdilution/ MRAE | 0.5 µg/mL | Tigecycline 0.12 µg/mL | [40] | |
| (7S,11S)-(+)-12-Hydroxysydonic acid (5) | Broth microdilution/S. aureus | 0.5 µg/mL | Tigecycline 0.06 µg/mL | [40] |
| Broth microdilution/ MRSA | 1 µg/mL | Tigecycline 0.25 µg/mL | [40] | |
| Broth microdilution/S. epidermidis | 0.25 µg/mL | Tigecycline 0.03 µg/mL | [40] | |
| Broth microdilution/ MRAE | 0.5 µg/mL | Tigecycline 0.12 µg/mL | [40] | |
| (11S,14S)-Cyclo-(L-Trp-L-Phe) (110) | Broth microdilution/S. aureus | 0.25 µg/mL | Tigecycline 0.06 µg/mL | [40] |
| Broth microdilution/ MRSA | 1 µg/mL | Tigecycline 0.25 µg/mL | [40] | |
| Broth microdilution/S. epidermidis | 0.12 µg/mL | Tigecycline 0.03 µg/mL | [40] | |
| Broth microdilution/ MRAE | 0.5 µg/mL | Tigecycline 0.12 µg/mL | [40] | |
| Citrinin (169) | Microplate assay/E. coli | 8 µg/mL | Chloramphenicol 1 µg/mL | [69] |
| Microplate assay/Micrococcus luteus | 16 µg/mL | Chloramphenicol 2 µg/mL | [69] | |
| Microplate assay/Vibrio parahaemolyticus | 8 µg/mL | Chloramphenicol 2 µg/mL | [69] | |
| Penicitrinol A (170) | Microplate assay/E. coli | 8 µg/mL | Chloramphenicol 1 µg/mL | [69] |
| Microplate assay/Micrococcus luteus | 4 µg/mL | Chloramphenicol 2 µg/mL | [69] | |
| Microplate assay/Vibrio parahaemolyticus | 8 µg/mL | Chloramphenicol 2 µg/mL | [69] | |
| Antituberculosis (IC50) | ||||
| Sydowiol A (166) | M. tuberculosis protein tyrosine phosphatase inhibitor | 14.0 μg/mL | - | [37] |
| Sydowiol B (167) | 24.0 μg/mL | - | [37] | |
| Anti-microalgae (IC50) | ||||
| (7S)-Flavilane A (53) | Broth microdilution/ Prorocentrum micans | 4.6 µg/mL | CuSO4 2.7 µg/mL | [38] |
| Broth microdilution/ Prorocentrum minimum | 2.4 µg/mL | CuSO4 2.2 µg/mL | [38] | |
| (7S)- 4-Iodo-flavilane A (54) | Broth microdilution/ Prorocentrum micans | 11.0 µg/mL | CuSO4 2.7 µg/mL | [38] |
| Broth microdilution/ Prorocentrum minimum | 1.3 µg/mL | CuSO4 2.2 µg/mL | [38] | |
| Bisviolaceol II (165) | Broth microdilution/ Prorocentrum minimum | 5.2 µg/mL | CuSO4 2.2 µg/mL | [38] |
Table 11.
Anti-influenza virus metabolites reported from Aspergillus sydowii.
| Compound Name | Virus/Assay | Biological Results (IC50) | Ref. | |
|---|---|---|---|---|
| Compound | Positive Control | |||
| 7-Deoxy-7,14-didehydrosydonic acid (8) | Puerto Rico/8/34 (H1N1)/Pseudovirus neutralization and MTT | 7.07 µM | Ribavirin 2.53 µM | [35] |
| cyclo-12-Hydroxysydonic acid (22) | Puerto Rico/8/34 (H1N1)/Pseudovirus neutralization and MTT | 8.89 µM | Ribavirin 2.53 µM | [35] |
| Aichi/2/68 (H3N2)/Pseudovirus neutralization and MTT | 36.41 µM | Ribavirin 6.23 µM | [35] | |
| FM-1/1/47(H1N1)/Pseudovirus neutralization and MTT | 24.46 µM | Ribavirin 3.97 µM | [35] | |
| 2-Hydroxy-1-(hydroxymethyl)-8-methoxy-3-methyl-9H-xanthen-9-one (80) | Puerto Rico/8/34 (H1N1)/Pseudovirus neutralization and MTT | 4.70 µM | Ribavirin 2.53 µM | [35] |
| FM-1/1/47 (H1N1)/Pseudovirus neutralization and MTT | 4.04 µM | Ribavirin 3.97 µM | [35] | |
| 2-Hydroxy-1-(hydroxymethyl)-7,8-dimethoxy-3-methyl-9H-xanthen-9-one (81) | Puerto Rico/8/34 (H1N1)/Pseudovirus neutralization and MTT | 2.17 µM | Ribavirin 2.53 µM | [35] |
| Emodic acid (92) | Puerto Rico/8/34 (H1N1)/Pseudovirus neutralization and MTT | 2.00 µM | Ribavirin 2.53 µM | [35] |
| Aichi/2/68 (H3N2)/Pseudovirus neutralization and MTT | 17.53 µM | Ribavirin 6.23 µM | [35] | |
| FM-1/1/47(H1N1)/Pseudovirus neutralization and MTT | 5.37 µM | Ribavirin 3.97 µM | [35] | |
| Parietinic acid (93) | Puerto Rico/8/34 (H1N1)/Pseudovirus neutralization and MTT | 7.88 µM | Ribavirin 2.53 µM | [35] |
| Aichi/2/68 (H3N2)/Pseudovirus neutralization and MTT | 30.09 µM | Ribavirin 6.23 µM | [35] | |
| FM-1/1/47(H1N1)/Pseudovirus neutralization and MTT | 39.60 µM | Ribavirin 3.97 µM | [35] | |
| Questin (94) | Puerto Rico/8/34 (H1N1)/Pseudovirus neutralization and MTT | 1.92 µM | Ribavirin 2.53 µM | [35] |
| Aichi/2/68 (H3N2)/Pseudovirus neutralization and MTT | 9.62 µM | Ribavirin 6.23 µM | [35] | |
| FM-1/1/47(H1N1)/Pseudovirus neutralization and MTT | 11.1 µM | Ribavirin 3.97 µM | [35] | |
| 1,6,8-Trihydroxy-3-methylanthraquinone (95) | Aichi/2/68 (H3N2)/Pseudovirus neutralization and MTT | 9.72 µM | Ribavirin 6.23 µM | [35] |
| FM-1/1/47(H1N1)/Pseudovirus neutralization and MTT | 18.48 µM | Ribavirin 3.97 µM | [35] | |
| Bisdethiobis(methylthio)-acetylaranotin (116) | Puerto Rico/8/34 (H1N1)/Pseudovirus neutralization and MTT | 34.60 µM | Ribavirin 2.53 µM | [35] |
| Aichi/2/68 (H3N2)/Pseudovirus neutralization and MTT | 24.56 µM | Ribavirin 6.23 µM | [35] | |
| FM-1/1/47(H1N1)/Pseudovirus neutralization and MTT | 44.08 µM | Ribavirin 3.97 µM | [35] | |
| Citrinin (169) | H5N1/Influenza neuraminidase inhibition screen kit | 45.6 nM | Oseltamivir 3.6 nM | [69] |
| Penicitrinol A (170) | H5N1/Influenza neuraminidase inhibition screen kit | 21.2 nM | Oseltamivir 3.6 nM | [69] |
| seco-Penicitrinol A (171) | H5N1/Influenza neuraminidase inhibition screen kit | 24.7 nM | Oseltamivir 3.6 nM | [69] |
| Penicitrinol L (172) | H5N1/Influenza neuraminidase inhibition screen kit | 41.5 nM | Oseltamivir 3.6 nM | [69] |
| Penicitrinone A (173) | H5N1/Influenza neuraminidase inhibition screen kit | 12.9 nM | Oseltamivir 3.6 nM | [69] |
| Penicitrinone F (174) | H5N1/Influenza neuraminidase inhibition screen kit | 18.5 nM | Oseltamivir 3.6 nM | [69] |
| Sydocyclopropane A (203) | WSN/33 (H1N1)/Cytopathic effect reduction/A/WSN/33 (H1N1) | 26.7 μM | Oseltamivir 18.1 μM | [42] |
| Sydocyclopropane B (204) | Cytopathic effect reduction/A/WSN/33 (H1N1) | 29.5 μM | Oseltamivir 18.1 μM | [42] |
| Hamavellone B (207) | Cytopathic effect reduction/A/WSN/33 (H1N1) | 35.8 μM | Oseltamivir 18.1 μM | [42] |
| 3,7-Dihydroxy-1,9-dimethyldibenzofuran (234) | Puerto Rico/8/34 (H1N1)/Pseudovirus neutralization and MTT | 1.31 µM | Ribavirin 2.53 µM | [35] |
| Aichi/2/68 (H3N2)/Pseudovirus neutralization and MTT | 1.24 µM | Ribavirin 6.23 µM | [35] | |
| FM-1/1/47(H1N1)/Pseudovirus neutralization and MTT | 2.84 µM | Ribavirin 3.97 µM | [35] | |
Table 12.
Anti-inflammatory metabolites reported from Aspergillus sydowii.
| Compound Name | Assay | Biological Results | Ref. | |
|---|---|---|---|---|
| Compound | Positive Control | |||
| (S)-(+)-Sydonic acid (1) | Inhibition of superoxide anion | 17.82 μM (IC50) | Sorafenib 1.27 μM (IC50) | [54] |
| (7S,11S)-(+)-12-Hydroxysydonic acid (5) | Inhibition of superoxide anion | 31.95 μM (IC50) | Sorafenib 1.27 μM (IC50) | [54] |
| Aspergillusene A (42) | Inhibition of superoxide anion | 6.11 μM (IC50) | Sorafenib 1.27 μM (IC50) | [54] |
| Inhibition of elastase release | 8.80 μM (IC50) | Sorafenib 1.27 μM (IC50) | [54] | |
| (+)-(7S)-Sydonol (45) | Inhibition of superoxide anion | 5.23 μM (IC50) | Sorafenib 1.27 μM (IC50) | [54] |
| Inhibition of elastase release | 16.39 μM (IC50) | Sorafenib 1.27 μM (IC50) | [54] | |
| (7S)-(+)-7-O-Methylsydonol (46) | Inhibition of superoxide anion | 13.80 μM (IC50) | Sorafenib 1.27 μM (IC50) | [54] |
| Anhydrowaraterpol B (49) | Inhibition of superoxide anion | 21.52 μM (IC50) | Sorafenib 1.27 μM (IC50) | [54] |
| Sydowinin B (71) | Inhibition of superoxide anion | 21.20 μM (IC50) | Sorafenib 1.27 μM (IC50) | [54] |
| Inhibition of elastase release | 12.62 μM (IC50) | Sorafenib 1.27 μM (IC50) | [54] | |
| (7R,8R)-AGI-B4 (88) | Inhibition of superoxide anion | 6.00 μM (IC50) | Sorafenib 1.27 μM (IC50) | [54] |
| Inhibition of elastase release | 6.60 μM (IC50) | Sorafenib 1.27 μM (IC50) | [54] | |
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Ibrahim, S.R.M.; Mohamed, S.G.A.; Alsaadi, B.H.; Althubyani, M.M.; Awari, Z.I.; Hussein, H.G.A.; Aljohani, A.A.; Albasri, J.F.; Faraj, S.A.; Mohamed, G.A. Secondary Metabolites, Biological Activities, and Industrial and Biotechnological Importance of Aspergillus sydowii. Mar. Drugs 2023, 21, 441. https://doi.org/10.3390/md21080441
AMA Style
Ibrahim SRM, Mohamed SGA, Alsaadi BH, Althubyani MM, Awari ZI, Hussein HGA, Aljohani AA, Albasri JF, Faraj SA, Mohamed GA. Secondary Metabolites, Biological Activities, and Industrial and Biotechnological Importance of Aspergillus sydowii. Marine Drugs. 2023; 21(8):441. https://doi.org/10.3390/md21080441
Chicago/Turabian StyleIbrahim, Sabrin R. M., Shaimaa G. A. Mohamed, Baiaan H. Alsaadi, Maryam M. Althubyani, Zainab I. Awari, Hazem G. A. Hussein, Abrar A. Aljohani, Jumanah Faisal Albasri, Salha Atiah Faraj, and Gamal A. Mohamed. 2023. "Secondary Metabolites, Biological Activities, and Industrial and Biotechnological Importance of Aspergillus sydowii" Marine Drugs 21, no. 8: 441. https://doi.org/10.3390/md21080441
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