Skip to main content

Advertisement

SpringerLink
Log in

Biotechnological production and application of ganoderic acids

  • Mini-Review
  • Published:
Applied Microbiology and Biotechnology Aims and scope Submit manuscript

Abstract

Ganoderic acids (GAs), a kind of highly oxygenated lanostane-type triterpenoids, are important bioactive constituents of the famous medicinal mushroom Ganoderma lucidum. They have received wide attention in recent years due to extraordinarily pharmacological functions. Submerged fermentation of G. lucidum is viewed as a promising technology for production of GAs, and substantial efforts have been devoted to process development for enhancing GA production in the last decade. This article reviews recent publication about fermentative production of GAs and their potential applications, especially the progresses toward manipulation of fermentation conditions and bioprocessing strategies are summarized. The biosynthetic pathway of GAs is also outlined.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Abe I, Rohmer M, Prestwich GD (1993) Enzymatic cyclization of squalene and oxidosqualene to sterols and triterpenes. Chem Rev 93:2189–2206

    Article  CAS  Google Scholar 

  • Akihisa T, Nakamura Y, Tagata M, Tokuda H, Yasukawa K, Uchiyama E, Suzuki T, Kimura Y (2007) Anti-inflammatory and anti-tumor-promoting effects of triterpene acids. Chem Biodivers 4:224–231

    Article  CAS  Google Scholar 

  • Boh B, Berovic M, Zhang J, Zhi-Bin L (2007) Ganoderma lucidum and its pharmaceutically active compounds. Biotechnol Annu Rev 13:265–301

    Article  CAS  Google Scholar 

  • Chen RY, Yu DQ (1990) Progress of studies on the chemical constituents of Ganoderma triterpenes. Acta Pharm Sin 25:940–953

    CAS  Google Scholar 

  • Chen NH, Zhong JJ (2009) Ganoderic acid Me induces G1 arrest in wild-type p53 human tumor cells while G1/S transition arrest in p53-null cells. Process Biochem 44:928–933

    Article  CAS  Google Scholar 

  • Chen NH, Liu JW, Zhong JJ (2008) Ganoderic acid Me inhibits tumor invasion through down-regulating matrix metalloproteinases 2/9 gene expression. J Pharmacol Sci 108:212–216

    Article  CAS  Google Scholar 

  • Ding YX, Ou-Yang X, Shang CH, Ren A, Shi L, Li YX, Zhao MW (2008) Molecular cloning, characterization, and differential expression of a farnesyl-diphosphate synthase gene from the basidiomycetous fungus Ganoderma lucidum. Biosci Biotechnol Biochem 72:1571–1579

    Article  CAS  Google Scholar 

  • El-Mekkaway SR, Meselhy M, Nakamura N, Tezuka Y, Hattori M, Kakiuchi N, Shimotohno K, Kawahata T, Otake T (1998) Anti-HIV-1 and anti-HIV-protease substances from Ganoderma lucidum. Phytochemistry 49:1651–1657

    Article  Google Scholar 

  • Fang QH, Zhong JJ (2002a) Submerged fermentation of higher fungus Ganoderma lucidum for production of valuable bioactive metabolites-ganoderic acid and polysaccharide. Biochem Eng J 10:61–65

    Article  CAS  Google Scholar 

  • Fang QH, Zhong JJ (2002b) Effect of initial pH on production of ganoderic acid and polysaccharide by submerged fermentation of Ganoderma lucidum. Process Biochem 37:769–774

    Article  CAS  Google Scholar 

  • Fang QH, Zhong JJ (2002c) Two-Stage culture process for improved production of ganoderic acid by liquid fermentation of higher fungus Ganoderma lucidum. Biotechnol Prog 18:51–54

    Article  CAS  Google Scholar 

  • Fang QH, Tang YJ, Zhong JJ (2002) Significance of inoculation density control in production of polysaccharide and ganoderic acid by submerged culture of Ganoderma lucidum. Process Biochem 37:1375–1379

    Article  CAS  Google Scholar 

  • Gong HG, Zhong JJ (2005) Hydrodynamic shear stress affect cell growth and metabolite production by medicinal mushroom Ganoderma lucidum. Chin J Chem Eng 13:426–428

    CAS  Google Scholar 

  • Guesnet J, Guezennec L, Anne BS (2003) Use of ganoderic acids as cosmetic agents and for treating or preventing skin disorder. EP 1434565

  • Hajjaj H, Mace C, Roberts M, Niederberger P, Fay LB (2005) Effect of 26-oxygenosterols from Ganoderma lucidum and their activity as cholesterol synthesis inhibitors. Appl Environ Microbiol 71:3653–3658

    Article  CAS  Google Scholar 

  • Hirotani M, Furuya T (1990) Changes of the triterpenoid patterns during formation of the fruit body in Ganoderma lucidum. Phytochemistry 29:3767–3771

    Article  CAS  Google Scholar 

  • Hirotani M, Ino C, Furuya T, Shiro M (1986) Ganoderic acids T, S and R, new triterpenoids from the cultured mycelia of Ganoderma lucidum. Chem Pharm Bull 34:2282–2285

    CAS  Google Scholar 

  • Hirotani M, Asaka I, Ino C, Furuya T, Shiro M (1987) Ganoderic acid derivatives and ergosta-4, 7, 22-triene-3, 6-dione from Ganoderma lucidum. Phytochemistry 36:3797–2803

    Google Scholar 

  • Hirotani M, Asaka I, Furuya T (1990) Investigation of the biosynthesis of 3-hydroxy triterpenoids, ganoderic acids T and S by application of a feeding experiment using [1, 2–13C2]acetate. J Chem Soc Perkin Trans 1:2751–2754

    Article  Google Scholar 

  • Hirotani M, Ino C, Furuya T (1993) Comparative study of the strain-specific triterpenoid components of Ganoderm lucidum. Phytochemistry 33:379–382

    Article  CAS  Google Scholar 

  • Jiang JH, Grieb B, Thyagarajan A, Sliva D (2008) Ganoderic acids suppress growth and invasive behavior of breast cancer cells by modulating AP-1 and NF-κb signaling. Int J Mol Med 21:577–584

    CAS  Google Scholar 

  • Kabir Y, Kimura S, Tamura T (1988) Dietary effect of Ganoderma lucidum mushroom on blood pressure and lipid levels in spontaneously hypertensive rats. J Nat Sci Vitaminol 34:433–438

    CAS  Google Scholar 

  • Kimura Y, Taniguchi M, Baba K (2002) Antitumor and antimetastatic effects on liver of triterpenoid fractions of Ganoderma lucidum: mechanism of action and isolation of an active substance. Anticancer Res 22:3309–3318

    CAS  Google Scholar 

  • Kohda G, Tokumoto W, Sakamoto K, Fujii M, Hirai Y, Yamasaki K, Komoda Y, Nakamura H, Ishihara S (1985) The biologically active constituents of Ganoderma lucidum (Fr.) Karst. histamine release-inhibitory triterpenes. Chem Pharm Bull 33:1367–1374

    CAS  Google Scholar 

  • Komoda Y, Shimizu M, Sonoda Y, Sato Y (1989) Ganoderic acid and derivatives as cholesterol synthesis inhibitors. Chem Pharm Bull 37:531–533

    CAS  Google Scholar 

  • Koyama K, Imaizumi T, Akiba M, Kinoshita K, Takahashi K, Suzuki A, Yano S, Horie S, Watanabe K, Naoi Y (1997) Antinociceptive components of Ganoderma lucidum. Planta Med 63:224–227

    Article  CAS  Google Scholar 

  • Kubota T, Asaka Y (1982) Structures of ganoderic acid A and B, two new lanostane type bitter triterpenes from Ganoderma lucidum (FR.) Karst. Helv Chim Acta 65:611–619

    Article  CAS  Google Scholar 

  • Leung SWS (2002) Lingzhi (Ganoderma) research-the past, present and future perspectives. In: Lin Zhi-bin (ed) Ganoderma: genetics, chemistry, pharmacology and therapeutics. Beijing, Beijing Medical University Press, pp 1–9

    Google Scholar 

  • Li CH, Chen PY, Chang M, Kan LS, Fang WH, Tsai KS, Lin SB (2005) Ganoderic acid X, a lanostanoid triterpene, inhibits topoisomerases and induces apoptosis of cancer cells. Life Sci 77:252–265

    Article  CAS  Google Scholar 

  • Li N, Liu XH, Zhou J, Li YX, Zhao MW (2006) Analysis of influence of environmental conditions on ganoderic acid content in Ganoderma lucidum using orthogonal design. J Microbiol Biotechnol 16:1940–1946

    CAS  Google Scholar 

  • Liang CX, Li YB, Xu JW, Wang JL, Miao XL, Tang YJ, Gu TY, Zhong JJ (2010) Enhanced biosynthetic gene expressions and production of ganoderic acids in static liquid culture of Ganoderma lucidum under phenobarbital induction. Appl Microbiol Biotechnol 86:1367–1374 doi:10.1007/s00253-009-2415-8

    Article  CAS  Google Scholar 

  • Lin LJ, Shiao MS, Yeh SF (1987) Seven new triterpenes from Ganoderma lucidum. J Nat Prod 51:918–924

    Article  Google Scholar 

  • Liu J, Shiono J, Shimizu K, Kukita A, Kukita T, Kondo R (2009) Ganoderic acid DM: anti-androgenic osteoclastogenesis inhibitor. Bioorg Med Chem Lett 19:2154–2157

    Article  CAS  Google Scholar 

  • Luo J, Lin ZB (2002) Advances of pharmacological effects of triterpenes from Ganoderma lucidum. Acta Pharm Sin 37:574–578

    CAS  Google Scholar 

  • Min BS, Nakamura N, Bae KW Miyashiro H, Hattori M (1998) Triterpenes from the spores of Ganoderma lucidum and their inhibitory activity against HIV-1 protease. Chem Pharm Bull 46:1607–1612

    CAS  Google Scholar 

  • Min BS, Gao JJ, Nakamura N, Hattori M (2000) Triterpenes from the spores of Ganoderma lucidum and their cytotoxicity against Meth-A and LLC tumour cell. Chem Pharm Bull 48:1026–1033

    CAS  Google Scholar 

  • Morigiwa A, Kitabatake K, Fujimoto Y, Ikekawa N (1986) Angiotensin converting enzyme-inhibitory triterpenes from Ganoderma lucidum. Chem Pharm Bull 34:3025–3028

    CAS  Google Scholar 

  • Nishitoba T, Sato H, Shirasu S, Sakamura S (1987a) Novel triterpenoids from the mycelia mat at the previous stage of fruiting of Ganoderma lucidum. Agric Biol Chem 51:619–622

    CAS  Google Scholar 

  • Nishitoba T, Sato H, Sakamura S (1987b) Novel mycelia components, ganoderic acid Mg, Mh, Mi, Mj and Mk, from the fungus Ganoderma lucidum. Agric Biol Chem 51:1149–1153

    CAS  Google Scholar 

  • Paterson RR (2006) Ganoderma—a therapeutic fungal biofactory. Phytochemistry 67:1985–2001

    Article  CAS  Google Scholar 

  • Sato N, Zhang Q, Ma CM, Hattori M (2009) Anti-human immunodeficiency virus-1 protease activity of new lanosane-type triterpenoids from Ganoderma sinense. Chem Pharm Bull 57:1076–1080

    Article  CAS  Google Scholar 

  • Seo HW, Hung TM, Na MK, Jung HJ, Kim JC, Choi JS, Kim JH, Lee HK, Lee IS, Bae KH, Hattori M, Min BS (2009) Steroids and triterpenes from the fruit bodies of Ganoderma lucidum and their anti-complement activity. Arch Pharm Res 32:1573–1579

    Article  CAS  Google Scholar 

  • Shang CH, Zhu F, Li N, Ou-Yang X, Shi L, Zhao MW, Li YX (2008) Cloning and characterization of a gene encoding HMG-CoA reductase from Ganoderma lucidum and its functional identification in yeast. Biosci Biotechnol Biochem 72:1333–1339

    Article  CAS  Google Scholar 

  • Shiao MS (1992) Triterpenoid natural products in the fungus Ganoderma lucidum. J Chin Chem Soc 39:669–674

    CAS  Google Scholar 

  • Shiao MS (2003) Natural products of the medicinal fungus Ganoderma lucidum: occurrence, biological activities and pharmacological functions. Chem Rec 3:172–180

    Article  CAS  Google Scholar 

  • Shiao MS, Lee LW (2005) Polysaccharides and oxygenated triterpenes in the fungus Ganoderma lucidum: Genomic approaches to their biological functions and biosynthesis. 230th ACS National Meeting. Washington, DC, p 154

    Google Scholar 

  • Shiao MS, Lin LJ, Yeh SF, Chou CS (1987) Two new triterpenes of the fungus Ganoderma lucidum. J Nat Prod 50:886–890

    Article  CAS  Google Scholar 

  • Shiao MS, Lin LJ, Yeh SF (1988a) Triterpenes in Ganoderma lucidum. Phytochemistry 27:2911–2914

    Article  CAS  Google Scholar 

  • Shiao MS, Lin LJ, Chen CS (1988b) Triterpenes in Ganoderma lucidum. Phytochemistry 27:873–875

    Article  Google Scholar 

  • Shiao MS, Lin LJ, Yeh SF, Chou CS (1989) Structures, biosynthesis and biological functions of oxygenated treterpenoids in Ganoderma lucidum. Phytochem Ecol 9:235–243

    CAS  Google Scholar 

  • Shiao MS, Lee KR, Lee JL, Cheng TW (1994) Natural products and biological activities of the Chinese medicinal fungus Ganoderma lucidum. Food Phytochemicals for Cancer Prevention II; ACS Symposium Series; American Chemical Society, Washington, DC, vol 547, pp 342–354

  • Sliva D (2004) Cellular and physiological effects of Ganoderma lucidum (Reishi). Mini Rev Med Chem 4:873–879

    CAS  Google Scholar 

  • Tang YJ, Zhong JJ (2002) Fed-batch fermentation of Ganoderma lucidum for hyperproduction of polysaccharide and ganoderic acid. Enzym Microb Tech 31:20–28

    Article  CAS  Google Scholar 

  • Tang YJ, Zhong JJ (2003a) Role of oxygen supply in submerged fermentation of Ganoderma lucidum for production of Ganoderma polysaccharide and ganoderic acid. Enzym Microb Tech 32:478–484

    Article  CAS  Google Scholar 

  • Tang YJ, Zhong JJ (2003b) Scale-up of a liquid static culture process for hyperproduction of ganoderic acid by the medicinal mushroom Ganoderma lucidum. Biotechnol Prog 19:1842–1846

    Article  CAS  Google Scholar 

  • Tang YJ, Zhong JJ (2004) Modeling the kinetics of cell growth and ganoderic acid production in liquid static cultures of the medicinal mushroom Ganoderma lucidum. Biochem Eng J 21:259–264

    Article  CAS  Google Scholar 

  • Tang W, Gu TY, Zhong JJ (2006a) Separation of targeted ganoderic acids from Ganoderma lucidum by reversed phase liquid chromatography with ultraviolet and mass spectrometry detections. Biochem Eng J 32:205–210

    Article  CAS  Google Scholar 

  • Tang W, Liu JW, Zhao WM, Zhong JJ (2006b) Ganoderic acid T from Ganoderma lucidum mycelia induces mitochondria mediated apoptosis in lung cancer cells. Life Sci 80:205–211

    Article  CAS  Google Scholar 

  • Tang YJ, Zhang W, Zhong JJ (2009) Performance analyses of a pH-shift and DOT-shift integrated fed-batch fermentation process for the production of ganoderic acid and Ganoderma polysaccharides by medicinal mushroom Ganoderma lucidum. Bioresource Technol 100:1852–1859

    Article  CAS  Google Scholar 

  • Toth JO, Luu B, Beck JP, Ourisson G (1983) Cytotoxic triterpenes from Ganoderma lucidum (polyporaceae): structures of ganoderic acids U-Z. Tetrahedron Lett 24:1081–1084

    Article  CAS  Google Scholar 

  • Tsujikura Y, Higuchi T, Miyamoto Y, Sato S (1992) Manufacture of ganoderic acid by fermentation of Ganoderma lucidum (in Japansese). Jpn Kokai Tokkyo Koho JP 04304890

  • Wagner R, Mitchell DA, Sassaki GL, Amazonas MALD, Berovic M (2003) Current techniques for the cultivation of Ganoderma lucidum for the production of biomass, ganoderic acid and Polysaccharides. Food Technol Biotechnol 41:371–382

    CAS  Google Scholar 

  • Wang F, Liu JK (2008) Highly oxygenated lanostane triterpenoids from the fungus Ganoderma applanatum. Chem Pharm Bull 56:1035–1307

    Article  CAS  Google Scholar 

  • Wang CN, Chen JC, Shiao MS, Wang CT (1989) The aggregation of human platelet induced by ganodermic acid S. Biochim Biophys Acta 986:151–160

    Article  CAS  Google Scholar 

  • Wang CN, Chen JC, Shiao MS, Wang CT (1991) The inhibition of human platelet function by ganodermic acids. Biochem J 277:189–197

    CAS  Google Scholar 

  • Wang G, Zhao J, Liu JW, Huang Y, Zhong JJ, Tang W (2007) Enhancement of IL-2 and IFN-γ expression and NK cells activity involved in the anti-tumor effect of ganoderic acid Me in vivo. Int Immunopharmacol 7:864–870

    Article  CAS  Google Scholar 

  • Wu TS, Shi LS, Kuo SC (2001) Cytotoxicity of Ganoderma lucidum triterpenes. J Nat Prod 64:1121–1122

    Article  CAS  Google Scholar 

  • Xu P, Ding ZY, Qian Z, Zhao CX, Zhang KC (2008) Improved production of mycelial biomass and ganoderic acid by submerged culture of Ganoderma lucidum SB97 using complex media. Enzyme Microb Technol 42:325–331

    Article  CAS  Google Scholar 

  • Xu JW, Xu YN, Zhong JJ (2010) Production of individual ganoderic acids and expression of biosynthetic genes in liquid static and shaking cultures of Ganoderma lucidum. Appl Microbiol Biotechnol 85:941–948

    Article  CAS  Google Scholar 

  • Yeh SF, Chou CS, Lin LJ, Shiao MS (1989) Biosynthesis of oxygenated triterpenoids in Ganoderma lucidum. Proc Natl Sci Council B ROC 13:119–127

    CAS  Google Scholar 

  • Yue QX, Cao ZW, Guan SH, Liu XH, Tao L, Wu WY, Li YX, Yang PY, Liu X, Guo DA (2008) Proteomics characterization of the cytotoxicity mechanism of ganoderic acid D and computerautomated estimation of the possible drug target network. Mol Cell Proteomics 7:949–961

    Article  CAS  Google Scholar 

  • Yue QX, Song XY, Ma C, Feng LX, Guan SH, Wu WY, Yang M, Jiang BH, Liu X, Cui YJ, Guo DA (2010) Effects of triterpenes from Ganoderma lucidum on protein expression profile of HeLa cells. Phytomedicine. doi:10.1016/j.phymed.2009.12.013

    Google Scholar 

  • Zhang W, Tang YJ (2008) A novel three-stage light irradiation strategy in the submerged fermentation of medicinal mushroom Ganoderma lucidum for the efficient production of ganoderic acid and Ganoderma polysaccharides. Biotechnol Prog 24:1249–1261

    Article  CAS  Google Scholar 

  • Zhang WX, Zhong JJ (2009) Impact of oxygen level in gaseous phase on gene transcription and ganoderic acid biosynthesis in liquid static cultures of Ganoderma lucidum. Biprocess Biosyst Eng. doi:10.1007/s00449-009-0379-9

    Google Scholar 

  • Zhang WX, Zhong JJ (2010) Effect of oxygen concentration in gas phase on sporulation and individual ganoderic acids accumulation in liquid static culture of Ganoderma lucidum. J Biosci Bioeng 109:37–40

    Article  CAS  Google Scholar 

  • Zhao MW, Liang WQ, Zhang DB, Wang N, Wang CG, Pan YJ (2007) Cloning and characterization of squalene synthase (SQS) gene from Ganoderma lucidum. J Microbiol Biotechnol 17:1106–1112

    CAS  Google Scholar 

  • Zhong JJ, Tang YJ (2004) Submerged cultivation of medicinal mushrooms for production of valuable bioactive metabolites. Adv Biochem Eng Biotechnol 87:25–59

    CAS  Google Scholar 

  • Zhou Y, Yang X, Yang Q (2006) Recent advances on triterpenes from Ganoderma mushroom. Food Rev Int 22:259–273

    Article  Google Scholar 

  • Zhu M, Chang Q, Wong LK, Chong FS, Li RC (1999) Triterpene antioxidants from Ganoderma lucidum. Phytother Res 13:529–531

    Article  CAS  Google Scholar 

  • Zhu LW, Zhong JJ, Tang YJ (2008) Significance of fungal elicitors on the production of ganoderic acid and Ganoderma polysaccharides by the submerged culture of medicinal mushroom Ganoderma lucidum. Process Biochem 43:1359–1370

    Article  CAS  Google Scholar 

Download references

Acknowledgment

Financial support from the National Natural Science Foundation of China (NSFC project nos. 20776084 and 30821005), the National High Technology R&D Program (863 project no. 2007AA021506), Shanghai Science and Technology Commission (project no. 08DZ1971900), and the Shanghai Leading Academic Discipline Project (project nos. B203 and B505) is gratefully acknowledged.

Author information

Authors and Affiliations

  1. Key Laboratory of Microbial Metabolism (Ministry of Education), School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dong-Chuan Road, Shanghai, 200240, China

    Jun-Wei Xu, Wei Zhao & Jian-Jiang Zhong

Authors
  1. Jun-Wei Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wei Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jian-Jiang Zhong
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jian-Jiang Zhong.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Xu, JW., Zhao, W. & Zhong, JJ. Biotechnological production and application of ganoderic acids. Appl Microbiol Biotechnol 87, 457–466 (2010). https://doi.org/10.1007/s00253-010-2576-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00253-010-2576-5

Keywords

Search

Navigation