Skip to main content

Advertisement

SpringerLink
Log in

Endophytic fungi: novel sources of anticancer lead molecules

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

Abstract

Cancer is a major killer disease all over the world and more than six million new cases are reported every year. Nature is an attractive source of new therapeutic compounds, as a tremendous chemical diversity is found in millions of species of plants, animals, and microorganisms. Plant-derived compounds have played an important role in the development of several clinically useful anti-cancer agents. These include vinblastine, vincristine, camptothecin, podophyllotoxin, and taxol. Production of a plant-based natural drug is always not up to the desired level. It is produced at a specific developmental stage or under specific environmental condition, stress, or nutrient availability; the plants may be very slow growing taking several years to attain a suitable growth phase for product accumulation and extraction. Considering the limitations associated with the productivity and vulnerability of plant species as sources of novel metabolites, microorganisms serve as the ultimate, readily renewable, and inexhaustible source of novel structures bearing pharmaceutical potential. Endophytes, the microorganisms that reside in the tissues of living plants, are relatively unstudied and offer potential sources of novel natural products for exploitation in medicine, agriculture and the pharmaceutical industry. They develop special mechanisms to penetrate inside the host tissue, residing in mutualistic association and their biotransformation abilities opens a new platform for synthesis of novel secondary metabolites. They produce metabolites to compete with the epiphytes and also with the plant pathogens to maintain a critical balance between fungal virulence and plant defense. It is therefore necessary that the relationship between the plants and endophytes during the accumulation of these secondary metabolites is studied. Insights from such research would provide alternative methods of natural product drug discovery which could be reliable, economical, and environmentally safe.

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.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Agusta A, Maehara S, Ohashi K, Simanjuntak P, Shibuya H (2005) Stereoselective oxidation at C-4 of flavans by the endophytic fungus Diaporthe sp. isolated from a tea plant. Chem Pharm Bull 53:1565–1569

    Article  CAS  Google Scholar 

  • Amna T, Puri SC, Verma V, Sharma JP, Khajuria RK, Musarrat J, Spiteller M, Qazi GN (2006) Bioreactor studies on the endophytic fungus Entrophospora infrequens for the production of an anticancer alkaloid camptothecin. Can J Microbiol 52:189–196

    Article  CAS  Google Scholar 

  • Arbuck SG, Christian MC, Fisherman JS, Cazenave LA, Sarosy G, Suffness M, Adams J, Canetta R, Cole KE, Friedman MA (1993) Clinical development of taxol. J Natl Cancer Inst Monogr 15:11–24

    Google Scholar 

  • Arnold AE, Maynard Z, Gilbert GS, Coley PD, Kursar TA (2000) Are tropical fungal endophytes hyperdiverse? Ecol Lett 3:267–274

    Article  Google Scholar 

  • Arnold AE, Mejía LC, Kyllo D, Rojas EI, Maynard Z, Robbins N, Herre EA (2003) Fungal endophytes limit pathogen damage in a tropical tree. Proc Natl Acad Sci USA 100:15649–15654

    Article  CAS  Google Scholar 

  • Asano T, Watase I, Sudo H, Kitazima M, Takayama H, Aimi N, Yamazaki SK (2004) Camptothecin production by in vitro cultures of Ophiorrhiza liukiuensis and O. kuroiwai. Plant Biotechnol 21:275–281

    Article  CAS  Google Scholar 

  • Ataei-Azimi A, Hashemloian BD, Ebrahimzadeh H, Majd A (2008) High in vitro production of ant-canceric indole alkaloids from periwinkle (Catharanthus roseus) tissue culture. Afr J Biotechnol 7:2834–2839

    CAS  Google Scholar 

  • Balandrin MJ, Klocke JA (1988) Medicinal, aromatic and industrial materials from plants, vol 4. In: Bajaj YPS (ed) Biotechnology in agriculture and forestry: medicinal and aromatic plant. Springer, Berlin, pp 1–36

    Google Scholar 

  • Banerjee S, Upadhyay N, Kukreja AK, Ahuja PS, Kumar S, Saha GC, Sharma RP, Chattopadhyay SK (1996) Taxanes from in vitro cultures of the Himalayan Yew Taxus wallichiana. Planta Med 62:333–335

    Article  CAS  Google Scholar 

  • Barnett CJ, Cullinan GJ, Gerzon K, Hoying RC, Jones WE, Newlon WM, Poore GA, Robison RL, Sweeney MJ, Todd GC, Dyke RW, Nelson RL (1978) Structure-activity relationships of dimeric Catharanthus alkaloids 1. Deacetyl vinblastine amide (vindesine) sulfate. J Med Chem 21:88

    Article  CAS  Google Scholar 

  • Berkowitz DB, Choi S, Maeng JH (2000) Enzyme-assisted asymmetric total synthesis of (−)-podophyllotoxin and (−)-picropodophyllin. J Org Chem 65:847–860

    Article  CAS  Google Scholar 

  • Bi J, Ji Y, Pan J, Yu Y, Chen H, Zhu X (2011) A new taxol-producing fungus (Pestalotiopsis malicola) and evidence for taxol as a transient product in the culture. Afr J Biotechnol 10:6647–6654

    CAS  Google Scholar 

  • Borges KB, Borges WDS, Pupo MT, Bonato PS (2008) Stereoselective analysis of thioridazine-2-sulfoxide and thioridazine-5-sulfoxide: an investigation of rac-thioridazine biotransformation by some endophytic fungi. J Pharm Biomed 46:945–952

    Article  CAS  Google Scholar 

  • Brown T, Tangen C, Flemming T, Macdonald J (1993) A phase II trial of taxol and granulocyte colony stimulating factor (G-CSF) in patients with adenocarcinoma of pancreas. Proc Am Soc Clin Onco 12 (abstracts) 200

    Google Scholar 

  • Bush EJ, Jones DW (1995) Asymmetric total synthesis of (−)-podophyllotoxin. J Chem Soc-Perkin Trans 1:151–155

    Google Scholar 

  • Cannon PF, Simmons CM (2002) Diversity and host preference of leaf endophytic fungi in the Iwokrama Forest Reserve, Guyana. Mycologia 94:210–220

    Article  Google Scholar 

  • Cao L, Huang J, Li J (2007) Fermentation conditions of Sinopodophyllum hexandrum endophytic fungus on production of podophyllotoxin. Food Fermen Ind 33:28–32

    CAS  Google Scholar 

  • Cau-uitz ML, Miranda-ham J, Coello-coello B, Chi LM, Pacheco, Loyola-Vargas OVM (1994) Indole alkaloid production by transformed and non-transformed root cultures of Catharanthus roseus. In Vitro Cell Dev Biol 30:84–88

    Google Scholar 

  • Chandra S, Bandopadhyay R, Kumar V, Chandra R (2010) Acclimatization of tissue cultured plantlets: from laboratory to land. Biotechnol Lett 32:1191–1205

    Article  CAS  Google Scholar 

  • Chattopadhyay S, Srivastava AK, Bhojwani SS, Bisaria VS (2001) Development of suspension culture of Podophyllum hexandrum for the production of podophyllotoxin. Biotechnol Lett 23:2063–2066

    Article  CAS  Google Scholar 

  • Chattopadhyay S, Srivastava AK, Bhojwani SS, Bisaria VS (2002) Production of podophyllotoxin by plant cell cultures of Podophyllum hexandrum in bioreactor. J Biosci Bioeng 93:215–220

    CAS  Google Scholar 

  • Chattopadhyay S, Bisaria VS, Bhojwani SS, Srivastava AK (2003a) Enhanced production of podophyllotoxin by fed-batch cultivation of Podophyllum hexandrum. Can J Chem Eng 81:1–8

    Article  Google Scholar 

  • Chattopadhyay S, Bisaria VS, Srivastava AK (2003b) Enhanced production of podophyllotoxin by Podophyllum hexandrum using in situ cell retention bioreactor. Biotechnol Prog 19:1026–1028

    Article  CAS  Google Scholar 

  • Chattopadhyay S, Mehra RS, Srivastava AK, Bhojwani SS, Bisaria VS (2003c) Effect of major nutrients on podophyllotoxin production in Podophyllum hexandrum suspension cultures. Appl Microbiol Biotechnol 60:541–546

    CAS  Google Scholar 

  • Constabel F, Gaudet-La Prairie P, Kurz WGW, Kutney JP (1982) Alkaloid production in Catharanthus roseus cell cultures. XII. Biosynthetic capacity of callus from original explants and regenerated shoots. Plant Cell Rep 1:139–142

    Article  Google Scholar 

  • Cragg GM, Newman DJ (2004/Rev.2006) Plants as a source of anti-cancer agents. In: E. Elisabetsky, N.L. Etkin (eds) Ethnopharmacology. Encyclopedia of Life Support Systems (EOLSS), developed under the Auspices of the UNESCO, Oxford, UK. EOLSS Publishers, Oxford. Available from: http://www.eolss.net

  • Cragg G, Suffness M (1988) Metabolism of plant-derived anti-cancer agents. Pharmacol Ther 37:425

    Article  CAS  Google Scholar 

  • Cragg GM, Boyd MR, Cardellina JH II, Grever MR, Schepartz S, Snader KM, Suffness M (1993) The search for new pharmaceutical crops. In: Janick J, Simon JE (eds) Drug discovery and development at the national cancer institute: new crops. Wiley, New York, pp 61–167

    Google Scholar 

  • Creasey WA (1979) The vinca alkaloids. In: Hahn FE (ed) Antibiotics, 5th edn. Springer, New York, pp 414–438

    Google Scholar 

  • Croteau R, Ketchum RB, Long RM, Kaspera R, Wildung MR (2006) Taxol biosynthesis and molecular genetics. Phytochem Rev 5:75–97

    Article  CAS  Google Scholar 

  • Damayanti Y, Lown JW (1998) Podophyllotoxins: current status and recent developments. Curr Med Chem 5:205–252

    Google Scholar 

  • De Carolis E, Chan F, Balsevich J, De Luca V (1990) Isolation and characterization of a 2-oxyglutarate dependent dioxygenase involved in the second-to-last step in vindoline biosynthesis. Plant Physiol 94:1323–1329

    Article  Google Scholar 

  • De Luca V, Fernandez JA, Campbell D, Kurz WGW (1988) Developmental regulation of enzymes of indole alkaloid biosynthesis in Catharanthus roseus. Plant Physiol 86:447–450

    Article  Google Scholar 

  • Debbab A, Aly AH, Edrada-Ebel RA, Müller Werner EG, Mosaddak M, Hakiki A, Rainer Ebel R, Proksch P (2009) Bioactive secondary metabolites from the endophytic fungus Chaetomium sp. isolated from Salvia officinalis growing in Morocco. Biotechnol Agron Soc Environ 13:229–234

    CAS  Google Scholar 

  • Deng BW, Liu KH, Chen WQ, Ding XW, Xie XC (2009) Fusarium solani Tax-3, a new endophytic taxol-producing fungus from Taxus chinensis. World J Microbiol Biotechnol 25:139–143

    Article  CAS  Google Scholar 

  • Einzig AI, Wiernik PH, Schwartz EL (1991) Taxol: a new agent active in melanoma and ovarian cancer. Cancer Treat Res 58:89–100

    Article  CAS  Google Scholar 

  • Ettinger DS (1992) Taxol in the treatment of lung cancer. In: Abstracts of Second National Cancer Institute Workshop on Taxol and Taxus, Alexandria, Virginia, pp 23–24

  • Eyberger AL, Dondapati R, Porter JR (2006) Endophyte fungal isolates from Podophyllum peltatum produce podophyllotoxin. J Nat Prod 69:1121–1124

    Article  CAS  Google Scholar 

  • Fett-Neto AG, DiCosmo F, Reynolds WF, Sakata K (1992) Cell culture of Taxus as a source of the antineoplastic drug taxol and related taxanes. Biotechnol 10:1572–1575

    Article  CAS  Google Scholar 

  • Flores HE, Sgrignoli PJ (1991) In vitro culture and precocious germination of Taxus embryos. In Vitro Cell Dev Biol 27:139–142

    Google Scholar 

  • Forastiere AA, Neuberg D, Taylor SG, DeConti R, Adams G (1993) Phase II evaluation of taxol in advanced head and neck cancer: an Eastern Cooperative Oncology Group Trial. J Natl Cancer Inst Monogr 15:181–184

    Google Scholar 

  • Frense D (2007) Taxanes: perspectives for biotechnological production. Appl Microbiol Biotechnol 73:1233–1240

    Article  CAS  Google Scholar 

  • Fröhlich J, Hyde KD, Petrini O (2000) Endophytic fungi associated with palms. Mycol Res 104:1202–1212

    Article  Google Scholar 

  • Furmanowa M, Syklowska-Baranek K (2000) Hairy root cultures of Taxus x media var. Hicksii Rehd. as a new source of paclitaxel and 10-deacetylbaccatin III. Biotechnol Lett 22:683–686

    Article  CAS  Google Scholar 

  • Gangadevi V, Muthumary J (2008) Isolation of Colletotrichum gloeosporioides: a novel endophytic taxol-producing fungus from the leaves of a medicinal plant, Justicia gendarussa. Mycol Balc 5:1–4

    Google Scholar 

  • Germaine K, Keogh E, Garcia-Cabellos G, Borremans B, Lelie D, Bara TC, Oeyen L, Vangronsveld J, Moore FP, Moore ERB, Campbell CD, Ryan D, Dowling DN (2004) Colonisation of poplar trees by gfp expressing bacterial endophytes. FEMS Microbiol Ecol 48:109

    Article  CAS  Google Scholar 

  • Giri A, Giri CC, Dhingra V, Narasu ML (2001) Enhanced podophyllotoxin production from Agrobacterium rhizogenes transformed cultures of Podophyllum hexandrum. Nat Prod Lett 15:229–235

    Article  CAS  Google Scholar 

  • Govindachari TR, Viswanathan N (1972) Alkaloids of Mappia foetida. Phytochemistry 11:3529–3531

    Article  CAS  Google Scholar 

  • Guo B, Li H, Zhang L (1998) Isolation of the fungus producing vinblastine. J Yunnan Univ (Nat Sci Edit) 20:214–215

    CAS  Google Scholar 

  • Guo BH, Wang YC, Zhou XW, Hu K, Tan F, Miao ZQ, Tang KX (2006) An endophytic taxol-producing fungus BT2 isolated from Taxus chinensis var. mairei. Afr J Biotechnol 5:875–877

    CAS  Google Scholar 

  • Gurudatt PS, Priti V, Shweta S, Ramesha BT, Ravikanth G, Vasudeva R, Amna T, Deepika S, Ganeshaiah KN, Shaanker RU, Puri S, Qazi N (2010) Attenuation of camptothecin production and negative relation between hyphal biomass and camptothecin content in endophytic fungal strains isolated from Nothapodytes nimmoniana Grahm (Icacinaceae). Curr Sci 98:1006–1010

    CAS  Google Scholar 

  • Himes RH, Kersey RN, Heller-Bettinger J, Samson FE (1976) Action of the vinca alkaloids vincristine, vinblastine, and desacetyl vinblastine amide on microtubules in vitro. Cancer Res 36:3798–3802

    CAS  Google Scholar 

  • Hirata K, Yamanaka A, Kurano N, Miyamoto K, Miura Y (1987) Production of indole alkaloids in multiple shoot culture of Cathranthus roseus (L). G. Don. Agric Biol Chem 51:1311–1317

    Article  CAS  Google Scholar 

  • Holmes FA, Walters RS, Theriault RL, Forman AD, Newton LK, Raber MN, Buzdar AU, Frye DK, Hortabagyi GN (1991) Phase II trial of taxol, an active drug in the treatment of metastatic breast cancer. J Natl Cancer Inst 83:1797–1805

    Article  CAS  Google Scholar 

  • Horowitz SB, Lothsteia L, Manfredi JJ, Mellado W, Parness J, Roy SN, Schiff PB, Sorbara L, Zeheb R (1986) Taxol: mechanism of action and resistance. Ann NY Acad Sci 466:733–743

    Article  Google Scholar 

  • Huang YJ, Wang JF, Li GL, Zheng Z, Su WJ (2001) Antitumor and antifungal activities in endophytic fungi isolated from pharmaceutical plants Taxus mairei, Cephalataxus fortunei and Torreya grandis. FEMS Immunol Med Microbiol 1:163–167

    Article  Google Scholar 

  • Hughes EH, Shanks JV (2002) Metabolic engineering of plants for alkaloid production. Metab Eng 4:41–48

    Article  CAS  Google Scholar 

  • Immaculate Nancy Rebecca A, Mukesh Kumar DJ, Srimathi S, Muthumary J, Kalaichelvan PT (2011) Isolation of phoma species from Aloe vera: an endophyte and screening the fungus for taxol production. World J Sci Technol 1:23–31

    Google Scholar 

  • Jackson DE, Dewick PM (1984) Aryltetralin lignans from Podophyllum hexandrum and Podophyllum peltatum. Photochemistry 23:1147–1152

    Article  CAS  Google Scholar 

  • Jacqueline VS, Sushi KJ, Rijhwani M, Vani RB, Ho CH (1999) Quantification of metabolic fluxes for metabolic engineering of plant products. In: Fu J et al (eds) Plant cell and tissue culture for the production of food ingredients. Kluwer Academic/Plenum Publishers, New York

    Google Scholar 

  • Jennewein S, Croteau R (2001) Taxol: biosynthesis, molecular genetics, and biotechnological applications. Appl Microbiol Biotechnol 57:13–19

    Article  CAS  Google Scholar 

  • Jennewein S, Rithner CD, Williams RM, Croteau RB (2001) Taxol biosynthesis: taxane 13-hydroxylase is a cytochrome P450-dependent monooxygenase. PNAS 98:13595–13600

    Article  CAS  Google Scholar 

  • Ji Y, Bi JN, Yan B, Zhu XD (2006) Taxol-producing fungi: a new approach to industrial production of taxol. Chin J Biotechnol 22:1–6

    Article  Google Scholar 

  • Kadkade PG (1982) Growth and podophyllotoxin production in callus tissues of Podophyllum peltatum. Plant Sci Lett 25:107–115

    Article  CAS  Google Scholar 

  • Kalidass C, Mohan VR, Daniel A (2010) Effect of auxin and cytokinin on vincristine production by callus cultures of Catharanthus roseus L. (Apocynaceae). Trop Subtrop Agroecosyst 12:283–288

    Google Scholar 

  • Karuppusamy S (2009) A review on trends in production of secondary metabolites from higher plants by in vitro tissue, organ and cell cultures. J Med Plant Res 3:1222–1239

    CAS  Google Scholar 

  • Kharwar RN, Verma VC, Strobel G, Ezra D (2008) The endophytic fungal complex of Catharanthus roseus (L.) G. Don. Curr Sci 95:228–233

    CAS  Google Scholar 

  • Khosroushahi AY, Valizadeh M, Ghasempour A, Khosrowshahli M, Naghdibadi H, Dadpour MR, Omidi Y (2006) Improved taxol production by combination of inducing factors in suspension cell culture of Taxus baccata. Cell Biol Int 30:262–269

    Article  CAS  Google Scholar 

  • Kim SU, Strobel GA, Ford E (1999) Screening of taxol-producing endophytic fungi from Ginkgo biloba and Taxus cuspidata in Korea. Agric Chem Biotechnol 42:97–99

    CAS  Google Scholar 

  • Kour A, Shawl AS, Rehman S, Sultan P, Qazi PH, Suden P, Khajuria RK, Verma V (2008) Isolation and identification of an endophytic strain of Fusarium oxysporum producing podophyllotoxin from Juniperus recurva. World J Microbiol Biotechnol 24:1115–1121

    Article  CAS  Google Scholar 

  • Kumaran RS, Kim HJ, Hur BK (2010) Taxol promising fungal endophyte, Pestalotiopsis species isolated from Taxus cuspidate. J Biosci Bioeng 110:541–546

    Article  CAS  Google Scholar 

  • Kumaran RS, Jung H, Kim HJ (2011) In vitro screening of taxol, an anticancer drug produced by the fungus, Colletotrichum capsici. Eng Life Sci 3:264–271

    Article  CAS  Google Scholar 

  • Kusari S, Lamshöft M, Spiteller M (2009a) Aspergillus fumigates Fresenius, an endophytic fungus from Juniperus communis L. Horstmann as a novel source of the anticancer pro-drug deoxypodophyllotoxin. J App Microbiol 107:1019–1030

    Article  CAS  Google Scholar 

  • Kusari S, Zuhlke S, Spiteller M (2009b) An endophytic fungus from Camptotheca acuminata that produces camptothecin and analogues. J Nat Prod 72:2–7

    Article  CAS  Google Scholar 

  • Kutney JP, Arimoto H, Hewitt GM, Jarvis TC, Sakata K (1991) Studies with plant cell cultures of Podophyllum peltatum L. I. Production of podophyllotoxin, deoxypodophyllotoxin, podophyllotoxone and 4′-demethylpodophyllotoxin. Heterocycles 32:2305–2309

    Article  CAS  Google Scholar 

  • Kwak SS, Choi MS, Park YG, Yoo JS, Liu JR (1995) Taxol content in the seeds of Taxus spp. Phytochemistry 40:29–32

    Article  CAS  Google Scholar 

  • Larran S, Mónaco C, Alippi HE (2001) Endophytic fungi in leaves of Lycopersicon esculentum Mill. World J Microbiol Biotechnol 17:181–184

    Article  Google Scholar 

  • Lee KH, Xiao Z (2003) Lignans in treatment of cancer and other diseases. Phytochem Rev 2:341–362

    Article  CAS  Google Scholar 

  • Lee JC, Yang X, Schwartz M, Strobel G, Clardy J (1995) The relationship between an endangered North American tree and an endophytic fungus. Chem Biol 2:721–727

    Article  CAS  Google Scholar 

  • Li JY, Strobel GA, Sidhu R, Hess WM, Ford EJ (1996) Endophytic taxol-producing fungi from bald cypress, Taxodium distichum. Microbiology 142:2223–2226

    Article  CAS  Google Scholar 

  • Li JY, Sidhu RS, Ford EJ, Long DM, Hess WM, Strobel GA (1998) The induction of taxol production in the endophytic fungus (Periconia sp.) from Torreya grandifolia. J Ind Microbiol Biotechnol 20:259–264

    Article  CAS  Google Scholar 

  • Li YC, Tao WY, Cheng L (2009) Paclitaxel production using co-culture of Taxus suspension cells and paclitaxel-producing endophytic fungi in a co-bioreactor. Appl Microbiol Biotechnol 83:233–239

    Article  CAS  Google Scholar 

  • Loyola-Vargas VM, Mendez-Zeel M, Monforte-Gonzalez M, Miranda-Ham ML (1992) Serpentine accumulation during greening in normal and tumor tissues of Catharanthus roseus. J Plant Physiol 140:213–217

    Article  CAS  Google Scholar 

  • Lu L, He J, Yu X, Li G, Zhang X (2006) Studies on isolation and identification of endophytic fungi strain SC13 from harmaceutical plant Sabina vulgaris Ant. and metabolites. Acta Agric Boreal-Occident Sin 15:85–89

    Google Scholar 

  • Majumder A, Jha S (2009) Biotechnological approaches for the production of potential anticancer leads podophyllotoxin and paclitaxel: an overview. J Bio Sci 1:46–69

    Google Scholar 

  • Markman M (1991) Taxol: an important new drug in the management of epithelial ovarian cancer. Yale J Biol Med 64:583–590

    CAS  Google Scholar 

  • McGuire WP, Rowinsky EK, Rosenshein NB, Grumbine FC, Ettinger DS, Armstrong DK, Donehower RC (1989) Taxol: a unique antineoplastic agent with significant activity in advanced ovarian epithelial neoplasms. Ann Int Med 11:273–279

    Google Scholar 

  • Min C, Wang X (2009) Isolation and identification of the 10-hydroxycamptothecin-producing endophytic fungi from Camptotheca acuminata Decne. Acta Bot Boreal-Occident Sin 29:614–617

    CAS  Google Scholar 

  • Moraes RM, Burandt C, Ganzera M, Li X, Khan I, Canel C (2001) The American mayapple revisited—Podophyllum peltatum—still a potential cash crop? Econ Bot 54:471–476

    Article  Google Scholar 

  • Nadeem M, Palni LMS, Kumar A, Nandi SK (2007) Podophyllotoxin content, above- and belowground biomass in relation to altitude in Podophyllum hexandrum populations from Kumaun region of the Indian Central Himalaya. Planta Med 73:388–391

    Article  CAS  Google Scholar 

  • Nadeem M, Mauji R, Pravej A, Ahmad MM, Mohammad A, Qurainy FA, Khan S, Abdin MZ (2012) Fusarium solani, P1, a new endophytic podophyllotoxin-producing fungus from roots of Podophyllum hexandrum. Afr J Microbiol Res 6:2493–2499

    CAS  Google Scholar 

  • O’Keefe BR, Mahady GB, Gills JJ, Beecher CWW (1997) Stable vindoline production in transformed cell cultures of Catharanthus roseus. J Nat Prod 60:261–264

    Article  Google Scholar 

  • Owellen RJ, Donigian DW, Hartke CA, Hains FO (1977) Correlation of biologic data with physicochemical properties among the vinca alkaloids and their congeners. Biochem Pharmacol 26:1213–1219

    Article  CAS  Google Scholar 

  • Padmanabha BV, Chandrashekar M, Ramesha BT, Hombe Gowda HC, Rajesh P, Gunaga SS, Vasudeva R, Ganeshaiah KN, Shaanker RU (2006) Patterns of accumulation of camptothecin, an anti-cancer alkaloid in Nothapodytes nimmoniana Graham., in the Western Ghats, India: implications for identifying high-yielding sources of the alkaloid. Curr Sci 90:95–99

    CAS  Google Scholar 

  • Pandi M, Manikandan R, Muthumary J (2010) Anticancer activity of fungal taxol derived from Botryodiplodia theobromae Pat., an endophytic fungus against 7,12 dimethyl benz(a)anthracene (DMBA)-induced mammary gland carcinogenesis in Sprague Dawley rats. Biomed Pharmacother 64:48–53

    Article  CAS  Google Scholar 

  • Pandi M, Kumaran RS, Choi YK, Kim HJ, Muthumary J (2011) Isolation and detection of taxol, an anticancer drug produced from Lasiodiplodia theobromae, an endophytic fungus of the medicinal plant Morinda citrifolia. Afr J Biotechnol 10:1428–1435

    CAS  Google Scholar 

  • Patel B, Das S, Prakash R, Yasir M (2010) Natural bioactive compound with anticancer potential. Int J Adv Pharm Sci 1:32–41

    Article  CAS  Google Scholar 

  • Penalva MA, Rowlands RT, Turner G (1998) The optimization of penicillin biosynthesis in fungi. Trends Biotechnol 16:483

    Article  CAS  Google Scholar 

  • Petrini O (1986) Taxonomy of endophytic fungi of aerial plant tissues. In: Fokkema NJ, Van den Heuvel (eds) Microbiology of the phyllopshere. Cambridge University Press, Cambridge, pp 175–187

    Google Scholar 

  • Petrini O (1991) Fungal endophytes of tree leaves. In: Andrews J, Hirano S (eds) Microbial ecology of leaves. Springer, New York, pp 179–197

    Chapter  Google Scholar 

  • Photita W, Lumyong S, Lumyong P, Hyde KD (2001) Endophytic fungi of wild banana (Musa acuminata) at Doi Suthep Pui National Park, Thailand. Mycol Res 105:1508–1513

    Article  Google Scholar 

  • Preeti V, Ramesha BT, Singh S, Ravikanth G, Ganeshaiah KN, Suryanarayanan TS, Shaanker RU (2009) How promising are endophytic fungi as alternative sources of plant secondary metabolites? Curr Sci 97:477–478

    Google Scholar 

  • Puri Nazir SC, Chawla AR (2006) The endophytic fungus Trametes hirsuta as a novel alternative source of podophyllotoxin and related aryl tetralin lignans. J Biotechnol 122:494–510

    Article  CAS  Google Scholar 

  • Puri SC, Verma V, Amna T, Qazi GN, Spiteller M (2005) An endophytic fungus from Nothapodytes foetida that produces camptothecin. J Nat Prod 68:1717–1719

    Article  CAS  Google Scholar 

  • Qiu D, Huang M, Fang X, Zhe C (1994) Isolation of an endophytic fungus associated with Taxus yunnanensis. Acta Mycol Sin 13:314–316

    Google Scholar 

  • Rehman S, Shawl AS, Kour A, Andrabi R, Sudan P, Sultan P, Verma V, Qazi GN (2008) An endophytic Neurospora sp. from Nothapodytes foetida producing camptothecin. Appl Biochem Microbiol 44:203–209

    Article  CAS  Google Scholar 

  • Rehman S, Shawl AS, Kour A, Sultan P, Ahmad K, Khajuria R, Qazi GN (2009) Comparative studies and identification of camptothecin produced by an endophyte at shake flask and bioreactor. Nat Prod Res 23:1050–1057

    Article  CAS  Google Scholar 

  • Roja G (2008) Micropropagation and production of camptothecin from in vitro plants of Ophiorrhiza rugosa var. decumbens. Nat Prod Res 22:1017–1023

    Article  CAS  Google Scholar 

  • Roth BJ, Yep BY, Wilding G, Kasimes B, McLeod D, Loehrer PJ (1993) Taxol in advanced hormone refractory carcinoma of the prostrate: a phase II trial of the Eastern Cooperative Oncology Group. Cancer 72:2457

    Article  CAS  Google Scholar 

  • Ruiz-Sanchez J, Flores-Bustamante ZR, Dendooven L, Favela-Torres E, Soca-Chafre G, Galindez-Mayer J, Flores-Cotera LB (2010) A comparative study of taxol production in liquid and solidstate fermentation with Nigrospora sp., a fungus isolated from Taxus globosa. J Appl Microbiol 109:2144–2150

    Article  CAS  Google Scholar 

  • Samuelsson G (1999) Drugs of natural origin, 4th edn. Swedish Pharmaceutical Press, Stockholm, p 487

    Google Scholar 

  • Saunders M, Kohn LM (2009) Evidence for alteration of fungal endophyte community assembly by host defense compounds. New Phytol 182:229–238

    Article  CAS  Google Scholar 

  • Schiff PB, Fant J, Auster LA, Horowitz SB (1978) Effects of taxol on cell growth and in vitro microtubule assembly. J Supramol Struct Suppl 8:328

    Google Scholar 

  • Schulz B, Boyle C, Draeger S, Rommert AK, Krohn K (2002) Endophytic fungi: a source of novel biologically active secondary metabolites. Mycol Res 106:996–1004

    Article  CAS  Google Scholar 

  • Shweta S, Zuehlke S, Ramesha BT, Priti V, Kumar PM, Ravikanth G, Spiteller M, Vasudeva R, Shaanker RU (2010) Endophytic fungal strains of Fusarium solani, from Apodytes dimidiate E. Mey. ex Arn (Icacinaceae) produce camptothecin, 10-hydroxycamptothecin and 9-methoxycamptothecin. Phytochem 71:117–122

    Article  CAS  Google Scholar 

  • Sohn H, Okos MR (1998) Paclitaxel (taxol): from Nutt to drug. J Microbiol Biotechnol 8:427–440

    CAS  Google Scholar 

  • Sreekanth D, Sushim GK, Syed A, Khan BM, Ahmed A (2011) Molecular and morphological characterization of a taxol-producing endophytic fungus (Gliocladium sp.) from Taxus baccata. Mycobiology 3:151–157

    Article  CAS  Google Scholar 

  • Srivastava V, Negi AS, Kumar KJ, Gupta MM, Khanuja SPS (2005) Plant-based anticancer molecules: a chemical and biological profile of some important leads. Bioorg Med Chem 13:5892–5908

    Article  CAS  Google Scholar 

  • Stierle A, Strobel G, Stierle D (1993) Taxol and taxane production by Taxomyces andreanae, an endophytic fungus of Pacific yew. Science 260:214–216

    Article  CAS  Google Scholar 

  • Strobel GA, Hess WM, Ford E, Sidhu RS, Yang X (1996) Taxol from fungal endophytes and the issue of biodiversity. J Ind Microbiol 17:417–423

    Article  CAS  Google Scholar 

  • Strobel GA, Hess WM, Li JY, Ford E, Sears J, Sidhu RS, Summerell B (1997) Pestalotiopsis guepinii, a taxol producing endophyte of the Wollemi Pine, Wollemia nobilis. Aust J Bot 45:1073–1082

    Article  CAS  Google Scholar 

  • Sun D, Ran X, Wang J (2008) Isolation and identification of a taxol producing endophytic fungus from Podocarpus. Acta Microbiol Sin 48:589–595

    CAS  Google Scholar 

  • Taha HS, El-Bahr MK, Seif-El-Nasr MM (2009) In vitro studies on Egyptian Catharanthus roseus (L.) G.Don. IV: manipulation of some amino acids as precursors for enhanced of indole alkaloids production in suspension cultures. Aust J Basic Appl Sci 3:3137–3144

    CAS  Google Scholar 

  • Tan RX, Zou WX (2001) Endophytes: a rich source of functional metabolites. Nat Prod Rep 18:448–459

    Article  CAS  Google Scholar 

  • Tejesvi MV, Nalini MS, Mahesh B, Prakash HS, Kini KR, Shetty HS, Ven S (2007) New hopes from endophytic fungal secondary metabolites. Bol Soc Quím Méx 1:19–26

    Google Scholar 

  • Tyler RT, Kurz WGW, Panchuk BD (1986) Photoautotrophic cell suspension cultures of periwinkle (Catharanthus roseus (L.) G. Don): transition from heterotrophic to photoautotrophic growth. Plant Cell Rep 3:195–198

    Article  Google Scholar 

  • Van Uden W, Pras N, Visser JF, Malingre TM (1989) Detection and identification of podophyllotoxin produced by cell cultures derived from Podophyllum hexandrum Royle. Plant Cell Rep 8:165–168

    Article  Google Scholar 

  • Van Uden W, Pras N, Malingre TM (1990) On the improvement of the podophyllotoxin production by phenylpropanoid precursor feeding to cell cultures of Podophyllum hexandrum Royle. Plant Cell Tiss Org Cult 23:217–224

    Google Scholar 

  • Vasquez-Flota F, De Carolis E, Alarco AM, De Luca V (1997) Molecular cloning and characterization of deacetoxyvindoline-4-hydroxylase, a 2-oxoglutarate dependent dioxygenase involved in the biosynthesis of vindoline in Catharanthus roseus (L.) G. Don. Plant Mol Biol 34:935–948

    Article  Google Scholar 

  • Verpoorte R, Van der Heijden R, Van Gulik WM, Ten Hoopen HJG (1991) Plant biotechnology for the production of alkaloids: present status and prospects. In: Brossi A (ed) The alkaloids, vol 40. Academic, San Diego, pp 1–187

    Google Scholar 

  • Verpoorte R, Van der Heijden R, Moreno PRH (1997) Biosynthesis of terpenoid indole alkaloids in Catharanthus roseus cells. In: Cordell GA (ed) The alkaloids, vol 49. Academic, San Diego, p 221

    Google Scholar 

  • Verza M, Arakawa NS, Lope NP, Kato MJ, Pupo MT, Said S, Carvalho I (2009) Biotransformation of a tetrahydrofuran lignin by the endophytic fungus Phomopsis Sp. J Braz Chem Soc 20:195–200

    Article  CAS  Google Scholar 

  • Vineesh VR, Fijesh PV, Jelly Louis C, Jaimsha VK, Padikkala J (2007) In vitro production of camptothecin (an anticancer drug) from mutant albino plants of Ophiorrhiza rugosa var. decumbens. Curr Sci 92:1216–1218

    CAS  Google Scholar 

  • Visalakchi S, Muthumary J (2010) Taxol (anticancer drug) producing endophytic fungi: an overview. Int J Pharma Biosci 1:1–9

    Google Scholar 

  • Wall ME, Wani MC, Cook CE, Palmer KH, McPhail AT, Sim GA (1966) Plant antitumour agents I. The isolation and structure of camptothecin, a novel alkaloidal leukemia and tumour inhibitor from Camptotheca acuminata. J Am Chem Soc 88:3888–3890

    Article  CAS  Google Scholar 

  • Wang Y, Dai CC (2011) Endophytes: a potential resource for biosynthesis, biotransformation, and biodegradation. Ann Microbiol 61:207–215

    Article  CAS  Google Scholar 

  • Wang Y, Tang KX (2011) A new endophytic taxol- and baccatin III-producing fungus isolated from Taxus chinensis var. mairei. Afr J Biotechnol 10:16379–16386

    CAS  Google Scholar 

  • Wang ZY, Zhong JJ (2002) Repeated elicitation enhances taxane production in suspension cultures of Taxus chinensis in bioreactors. Biotechnol Lett 24:445–448

    Article  Google Scholar 

  • Wang J, Lu H, Huang Z, Zheng Z, Su WA (1999) Taxol-producing endophytic fungus isolated from Taxus mairei and its antitumor activity. J Xiamen Univ (Nat Sci Edit) 38:485–487

    Google Scholar 

  • Wang J, Li G, Lu H, Zheng Z, Huang Y, Su W (2000) Taxol from Tubercularia sp. strain TF5, an endophytic fungus of Taxus mairei. FEMS Microbiol Lett 193:249–253

    Article  CAS  Google Scholar 

  • Wang C, Wu J, Mei X (2001a) Enhancement of taxol production and excretion in Taxus chinensis cell culture by fungal elicitation and medium renewal. Appl Microbiol Biotechnol 55:404–410

    Article  CAS  Google Scholar 

  • Wang JW, Zhang Z, Tan RX (2001b) Stimulation of artemisinin production in Artemisia annua hairy roots by the elicitor from the endophytic Colletotrichum sp. Biotechnol Lett 23:857–860

    Article  CAS  Google Scholar 

  • Wang JW, Xia ZH, Tan RX (2002) Elicitation on artemisinin biosynthesis in Artemisia annua hairy roots by the oligosaccharide extract from the endophytic Colletotrichum sp. B501. Acta Bot Sin 44:1233–1238

    CAS  Google Scholar 

  • Wang JW, Zheng LP, Tan RX (2007a) Involvement of nitric oxide in cerebroside-induced defense responses and taxol production in Taxus yunnanensis suspension cells. Appl Microbiol Biotechnol 75:1183–1190

    Article  CAS  Google Scholar 

  • Wang SW, Ma X, Ping WX, Zhou DP (2007b) Research advances on taxol production by microbe fermentation. Microbiology 34:561–565 (In Chinese)

    CAS  Google Scholar 

  • Wang YC, Guo BH, Miao ZQ, Tang KX (2007c) Transformation of taxol producing endophytic fungi by restriction enzyme-mediated integration (REMI). FEMS Microbiol Lett 273:253–259

    Article  CAS  Google Scholar 

  • Wang YT, Hui-Shan L, Wang PH (2008) Endophytic fungi from Taxus mairei in Taiwan: first report of Colletotrichum gloeosporioides as an endophyte of Taxus mairei. Bot Stud 49:39–43

    Google Scholar 

  • Wani MC, Taylor HL, Wall ME, Coggon P, McPhail AT (1971) Plant antitumour agents. VI. The isolation and structure of taxol, a novel antileukemic and antitumour agent from Taxus brevifolia. J Am Chem Soc 93:2325–2327

    Article  CAS  Google Scholar 

  • Wei Y, Zhou X, Liu L, Lu J, Wang Z, Yu G, Hu L, Lin J, Sun X, Tang K (2010) An efficient transformation system of taxolproducing endophytic fungus EFY-21 (Ozonium sp.). Afr J Biotechnol 9:1726–1733

    CAS  Google Scholar 

  • Wheeler NC, Jech K, Masters S (1992) Effects of genetic, epigenetic and environmental factors on taxol content in Taxus brevifolia and related species. J Nat Prod 55:432–440

    Article  CAS  Google Scholar 

  • Wilson D (1995) Endophyte—the evolution of a term, and clarifcation of its use and defnition. Oikos 73:274–276

    Article  Google Scholar 

  • Woo DD, Miao SYP, Pelayo JC, Woolf AS (1994) Taxol inhibits progression of congenital polycystic kidney disease. Nature 368:750–753

    Article  CAS  Google Scholar 

  • Xu F, Tao W, Cheng L, Guo L (2006) Strain improvement and optimization of the media of taxol-producing fungus Fusarium maire. Biochem Eng J 31:67–73

    Article  CAS  Google Scholar 

  • Yang X, Guo S, Zhang L, Shao H (2003) Selection of producing podophyllotoxin endophytic fungi from podophyllin plant. Nat Prod Res Dev 15:419–422

    CAS  Google Scholar 

  • Yang X, Zhang L, Guo B, Guo S (2004) Preliminary study of a vincristine- producing endophytic fungus isolated from leaves of Catharanthus roseus. Chin Tradit Herbal Drug 35:79–81

    CAS  Google Scholar 

  • Yukimune Y, Tabata H, Higashi Y, Hara Y (1996) Methyl jasmonate-induced overproduction of paclitaxel and baccatin III in Taxus cell suspension cultures. Nat Biotechnol 14:1129–1132

    Article  CAS  Google Scholar 

  • Zhang L, Guo B, Li H, Zeng S, Shao H, Gu S, Wei R (2000) Preliminary study on the isolation of endophytic fungus of Catharanthus roseus and its fermentation to produce products of therapeutic value. Chin Tradit Herbal Drug 31:805–807

    CAS  Google Scholar 

  • Zhang HC, Liu JM, Lu HY, Gao SL (2009) Enhanced flavonoid production in hairy root cultures of Glycyrrhiza uralensis Fisch by combining the over-expression of chalcone isomerase gene with the elicitation treatment. Plant Cell Rep 28:1205–1213

    Article  CAS  Google Scholar 

  • Zhang P, Liu TT, Zhou PP, Li ST, Yu LG (2011) Agrobacterium tumefaciens-mediated transformation of a taxol-producing endophytic fungus Cladosporium cladosporioides MD2. Curr Microbiol 62:1315–1320

    Article  CAS  Google Scholar 

  • Zhin-Lin Y, Chuan-chao D, Lian-qing C (2007) Regulation and accumulation of secondary metabolites in plant–fungus symbiotic system. Afr J Biotechnol 6:1266–1271

    Google Scholar 

  • Zhou X, Zhu H, Liu L, Lin J, Tang K (2010) A review: recent advances and future prospects of taxol-producing endophytic fungi. Appl Microbiol Biotechnol 86:1707–1717

    Article  CAS  Google Scholar 

  • Zikmundova M, Drandarov K, Bigler L, Hesse M, Werner C (2002) Biotransformation of 2-benzoxazolinone and 2-hydroxy-1,4-benzoxazin-3-one by endophytic fungi isolated from Aphelandra tetragona. Appl Environ Microbiol 10:4863–4870

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors wish to thank DBT, UGC, CSIR, and other government funding agencies for providing financial assistance to promote the research work. SC is also thankful to the BTISNet SubDIC (BT/BI/04/065/04) and Birla Institute of Technology, Mesra, Ranchi, for providing infrastructure facilities.

Author information

Authors and Affiliations

  1. Department of Biotechnology, Birla Institute of Technology, Mesra, Ranchi, 835215, Jharkhand, India

    Sheela Chandra

Authors
  1. Sheela Chandra
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sheela Chandra.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chandra, S. Endophytic fungi: novel sources of anticancer lead molecules. Appl Microbiol Biotechnol 95, 47–59 (2012). https://doi.org/10.1007/s00253-012-4128-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00253-012-4128-7

Keywords

Search

Navigation