Phytochemistry Reviews

, Volume 11, Issue 4, pp 507–522 | Cite as

Metabolites of endophytic fungi as novel source of biofungicide: a review



Endophytic fungi are known to harbour compound(s) beneficial for plant health as well as human health. Among the metabolites of agrochemical and pharmaceutical importance alkaloids are the major. Apart from alkaloids several terpernoids and steroids, isocoumarins and chromones, phenolics and volatiles have also been reported. Cryptocin and cytochalasins alkaloids were isolated during early phase of innovation and proved to be antifungal. Some of these metabolites produced by endophytic fungi were originally isolated from the host plants.


Antifungal Biofungicide Endophytic fungi Fungal metabolites 


  1. Abdou R, Scherlach K, Dahse H-M, Sattler I, Hertweck C (2010) Botryorhodines A-D, antifungal and cytotoxic depsidones from Botryosphaeria rhodina, an endophyte of the medicinal plant Bidens pilosa. Phytochemistry 71:110–116PubMedCrossRefGoogle Scholar
  2. Ahmed I, Hussain H, Schulz B, Draeger S, Padula D, Pescitelli G, Van Ree T, Krohn K (2011) Three new antimicrobial metabolites from the endophytic fungus Phomopsis sp. Eur J Org Chem pp 2867–2873Google Scholar
  3. Arunpanichlert J, Rukachaisirikul V, Sukpondma Y, Phongpaichit S, Tewtrakul S, Rungjindamai N, Sakayaroj J (2010) Azaphilone and isocoumarin derivatives from the endophytic fungus Penicillium sclerotiorum PSU-A13. Chem Pharm Bull 58:1033–1036PubMedCrossRefGoogle Scholar
  4. Betina Y (1992) Biological Effects of the Antibiotic Brefeldin-A (Decumbin, Cyanein, Ascotoxin, Synergisidin): a retrospective. Folia Microbiol 37:3–11CrossRefGoogle Scholar
  5. Brady SF, Wagenaar MM, Singh MP, Janso JE, Clardy J (2000a) The cytosporones, new octaketide antibiotics isolated from an endophytic fungus. Org Lett 2:4043–4046PubMedCrossRefGoogle Scholar
  6. Brady SF, Singh MP, Janso JE, Clardy J (2000b) Cytoskyrins A and B, new BIA active bisanthraquinones isolated from an endophytic fungus. Org Lett 2:4047–4049PubMedCrossRefGoogle Scholar
  7. Bush LP, Wilkinson HH, Schardl CL (1997) Bioprotective alkaloids of grass-fungal endophyte symbioses. Plant Physiol 114:1–7PubMedGoogle Scholar
  8. Cai X, Shan T, Li P, Huang Y, Xu L, Zhou L, Wang M, Jiang W (2009) Spirobisnaphthalenes from the endophytic fungus Dzf12 of Dioscorea zingiberensis and their antimicrobial activities. Nat Prod Commun 4:1469–1472PubMedGoogle Scholar
  9. Chen X, Sang X, Li S, Zhang S, Bai L (2010) Studies on a chlorogenic acid-producing endophytic fungi isolated from Eucommia ulmoides Oliver. J Ind Microbiol Biotechnol 37:447–454PubMedCrossRefGoogle Scholar
  10. Cole RJ, Kirksey JW, Dorner JW, Wilson DN, Johnson JC, Johnson JAN, Bedell DM, Springer JP, Chexal KK, Clardy JC, Cox RH (1977) Mycotoxins produced by Aspergillus fumigatus species isolated from molded silage. J Agric Food Chem 25:826–830PubMedCrossRefGoogle Scholar
  11. Dai J, Krohn K, Draeger S, Schulz B (2009) New naphthalene-chroman coupling products from the endophytic fungus, Nodulisporium sp. from Erica arboreal. Eur J Org Chem pp 1564–1569Google Scholar
  12. Ding G, Liu S, Guo L, Zhou Y, Che Y (2008) Antifungal metabolites from the plant endophytic fungus Pestalotiopsis foedan. J Nat Prod 71:615–618PubMedCrossRefGoogle Scholar
  13. Fu J, Zhou Y, Li H-F, Ye Y-H, Guo J-H (2011) Antifungal metabolites from Phomopsis sp. By254, an endophytic fungus in Gossypium hirsutum. Afr J Microbiol Res 5:1231–1236Google Scholar
  14. Gu W (2009) Bioactive metabolites from Alternaria brassicicola ML-P08, an endophytic fungus residing in Malus halliana. World J Microbiol Biotechnol 25:1677–1683CrossRefGoogle Scholar
  15. Gurney KA, Mantle PG (1993) Biosynthesis of 1-N-methylalbonoursin by an endophytic Streptomyces sp. isolated from perennial ryegrass. J Nat Prod 56:1194–1198CrossRefGoogle Scholar
  16. Harper JK, Arif AM, Ford EJ, Strobel GA, Porco JA, Tomer DP, O¢Neill KL, Grant DM (2003) Pestacin: a 1,3-dihydro isobenzofuran from Pestalotiopsis microspora possessing antioxidant and antimycotic activities. Tetrahedron 59:2471–2476CrossRefGoogle Scholar
  17. He H, Yang HY, Bigelis R, Solum EH, Greenstein M, Carter GT (2002) Pyrrocidines A and B, new antibiotics produced by a filamentous fungus. Tetrahedron Lett 43:1633–1636CrossRefGoogle Scholar
  18. Horn WS, Simmonds MSJ, Schwartz RE, Blaney WM (1995) Phomopsichalasin, a novel antimicrobial agent from an endophytic Phomopsis sp. Tetrahedron 51:3969CrossRefGoogle Scholar
  19. Huang WY, Cai YZ, Hyde KD, Corke H, Sun M (2008) Biodiversity of endophytic fungi associated with 29 traditional Chinese medicinal plants. Fungal Divers 33:61–75Google Scholar
  20. Hussain H, Krohn K, Draeger S, Meier K, Schulz B (2009) Bioactive chemical constituents of a sterile endophytic fungus from Meliotus dentatus. Rec Nat Prod 3:114–117Google Scholar
  21. Koshino H, Togia S, Terada SI, Yoshihara T, Sakamura S, Shimanuki T, Sato T, Tajimi A (1989a) New fungitoxic sesquiterpenoids, chokols A-G, from stromata of Epichloe typhina and the absolute configuration of chokol. Agric Biol Chem 53:789–796CrossRefGoogle Scholar
  22. Koshino H, Yoshihara T, Sakamura S, Shimanuki T, Sato T, Tajimi A (1989b) Novel C-11 epoxy fatty acid from stromata of Epichloe typhina on Phleum pratense. Agric Biol Chem 53:2527–2528CrossRefGoogle Scholar
  23. Li JY, Strobel GA (2001) Jesterone and hydroxy-jesterone antioomycete cyclohexenone epoxides from the endophytic fungus Pestalotiopsis jesteri. Phytochemistry 57:261–265PubMedCrossRefGoogle Scholar
  24. Li JY, Strobel G, Harper J, Lobkovsky E, Clardy J (2000) Cryptocin, a potent tetramic acid antimycotic from the endophytic fungus Cryptosporiopsis cf. quercina. Org Lett 2:767–770PubMedCrossRefGoogle Scholar
  25. Li JY, Harper JK, Grant DM, Tombe BO, Bashyal B, Hess WM, Strobel GA (2001) Ambuic acid, a highly functionalized cyclohexenone with antifungal activity from Pestalotiopsis spp. and Monochaetia sp. Phytochemistry 56:463–468PubMedCrossRefGoogle Scholar
  26. Li H-Q, Li X-J, Wang Y-L, Zhang Q, Zhang A-L, Gao J-M, Zhang X-C (2011) Antifungal metabolites from Chaetomium globosum, an endophytic fungus in Ginkgo biloba. Biochemi Syst Ecol 39:876–879CrossRefGoogle Scholar
  27. Liu L, Liu S, Chen X, Guo L, Che Y (2009) Pestalofones A-E, bioactive cyclohexanone derivatives from the plant endophytic fungus Pestalotiopsis fici. Bioorg Medi Chem 17:606–613CrossRefGoogle Scholar
  28. Lu H, Xou WX, Meng JC, Hu J, Tan RX (2000) New bioactive metabolites produced by Colletotrichum sp., an endophytic fungus in Artemisia annua. Plant Sci 151:67–73CrossRefGoogle Scholar
  29. Macías-Rubalcava ML, Hernández-Bautista BE, Jiménez-Estrada M, González MC, Glenn AE, Hanlin RT, Hernández-Ortega S, Saucedo-García A, Muria-González JM, Anaya AL (2008) Naphthoquinone spiroketal with allelochemical activity from the newly discovered endophytic fungus Edenia gomezpompae. Phytochemistry 69:1185–1196PubMedCrossRefGoogle Scholar
  30. Maddau L, Cabras A, Franceschini A, Linaldeddu BT, Crobu S, Roggio T, Pagnozzi D (2009) Occurrence and characterization of peptaibols from Trichoderma citrinoviride, an endophytic fungus of cork oak, using electrospray ionization quadrupole time-of-flight mass spectrometry. Microbiol 155:3371–3381CrossRefGoogle Scholar
  31. Mao B-Z, Huang C, Yang G-M, Chen Y-Z, Chen S-Y (2010) Separation and determination of the bioactivity of oosporein from Chaetomium cupreum. Afr J Biotechnol 9:5955–5961Google Scholar
  32. Oliveira CM, Silva GH, Regasini LO, Zanardi LM, Evangelista AH, Young MCM, Bolzani VS, Araujo AR (2009) Bioactive metabolites produced by Penicillium sp. 1 and sp.2, two endophytes associated with Alibertia macrophylla (Rubiaceae). Z Naturforsch C 64:824–830Google Scholar
  33. Oliveira CM, Regasini LO, Silva GH, Pfenning LH, Young MCM, Berlinck RGS, Bolzani VS, Araujo AR (2011) Dihydroisocoumarins produced by Xylaria sp. and Penicillium sp., endophytic fungi associated with Piper aduncum and Alibertia macrophylla. Phytochem Lett 4:93–96CrossRefGoogle Scholar
  34. Park JH, Choi GJ, Lee HB, Kim KM, Jung HS, Lee SW, Jang KS, Cho KY, Kim JC (2005) Griseofulvin from Xylaria sp. Strain F0010, and endophytic fungus of Abies holophylla and its antifungal activity against plant pathogenic fungi. J Microbiol Biotechnol 15:112–117Google Scholar
  35. Pelaez F, Cabello A, Platas G, Diez MT, del Val AG, Basilio A, Martan I, Vicente F, Bills GF, Giacobbe RA, Schwartz RE, Onishi JC, Meinz MS, Abruzzo GK, Flattery AM, Kong L, Kurtz MB (2000) The discovery of enfumafungin, a novel antifungal compound produced by an endophytic Hormonema species biological activity and taxonomy of the producing organisms. Syst Appl Microbiol 23:333–343PubMedCrossRefGoogle Scholar
  36. Qin S, Krohn K, Flörke U, Schulz B, Draeger S, Pescitelli G, Salvadori P, Antus S, Kurtán T (2009) Two new fusidilactones from the fungal endophyte Fusidium sp. Eur J Org Chem pp 3279–3284Google Scholar
  37. Schmeda-Hirschmann G, Hormazabal E, Astudillo L, Rodriguez JL and Theoduloz C (2005) Secondary metabolites from endophytic fungi isolated from the Chilean gymnosperm Prumnopitys andina (Lleuque). World J Microbiol Biotechnol 21:27–32Google Scholar
  38. Schulz B, Sucker J, Aust HJ, Krohen K, Ludewig K, Jones PG, Doring D (1995) Biologically active secondary metabolites of endophytic Pezicula sp. Mycol Res 99:1007–1015CrossRefGoogle Scholar
  39. Schulz B, Rommert AK, Dammann U, Aust HJ, Strack D (1999) The endophyte-host interaction: a balanced antagonism? Mycol Res 103:1275–1283CrossRefGoogle Scholar
  40. Siddiqui IN, Zahoor A, Hussain H, Ahmed I, Ahmad VU, Padula D, Draeger S, Schulz B, Meier K, Steinert M, Kurtán T, Flörke U, Pescitelli G, Krohn K (2011) Diversonol and blennolide derivatives from the endophytic fungus Microdiplodia sp.: absolute configuration of diversonol. J Nat Prod 74:365–373PubMedCrossRefGoogle Scholar
  41. Silva GH, Teles HL, Zanardi LM, Marx Young MC, Eberlin MN, Hadad R, Pfenning LH, Costa-Neto CM, Castro-Gamboa I, da Silva Bolzani V, Araújo AR (2006) Cadinane sesquiterpenoids of Phomopsis cassiae, an endophytic fungus associated with Cassia spectabilis (Leguminosae). Phytochemistry 67:1964–1969PubMedCrossRefGoogle Scholar
  42. Silva GH, De Oliveira CM, Teles HL, Pauletti PM, Castro-Gamboa I, Silva DHS, Bolzani VS, Young MCM, Costa-Neto CM, Pfenning LH, Berlinck RGS, Araujo AR (2010) Sesquiterpenes from Xylaria sp., an endophytic fungus associated with Piper aduncum (Piperaceae). Phytochem Lett 3:164–167CrossRefGoogle Scholar
  43. Song YC, Li H, Ye YH, Shan CY, Yang YM, Tan RX (2004) Endophytic naphthopyrone metabolites are co-inhibitors of xanthine oxidase, SW1116 cell and some microbial growths. FEMS Microbiol Lett 241:67–72PubMedCrossRefGoogle Scholar
  44. Strobel G (2006) Muscodor albus and its biological promise. J Ind Microbiol Biotechnol 33:514–522PubMedCrossRefGoogle Scholar
  45. Strobel GA, Miller RV, Martinez-Miller C, Condron MM, Teplow DB, Hess WM (1999) Cryptocandin, a potent antimycotic from the endophytic fungus Cryptosporiopsis cf. quercina. Microbiology 145:1919–1926PubMedCrossRefGoogle Scholar
  46. Strobel GA, Dirkse E, Sears J, Markworth C (2001) Volatile antimicrobials from Muscador albus, a novel endophytic fungus. Microbiology 147:2943–2950PubMedGoogle Scholar
  47. Tan RX, Zou WX (2001) Endophytes: a rich source of functional metabolites. Nat Prod Rep 18:448–459PubMedCrossRefGoogle Scholar
  48. Vurro M, Evidente A, Andolfi A, Zonuo MC, Giordano F, Motta A (1998) Brefeldin A and α, β-dehydrocurvularin, two phytotoxins from Alternaria zinniae, a biocontrol agent of Xanthium occidentale. Plant Sci 138:67–79CrossRefGoogle Scholar
  49. Wang J, Huang Y, Fang M, Zhang Y, Zheng Z, Zhao Y, Su W (2002) Brefeldin A, a cytotoxin produced by Paecilomyces sp. and Aspergillus clavatus isolated from Taxus mairei and Torreya grandis. FEMS Immunol Med Microbiol 34:51–57PubMedCrossRefGoogle Scholar
  50. Wang Y, Guo B, Miao Z, Tang K (2007) Transformation of taxol-producing endophytic fungi by restriction enzyme-mediated integration (REMI). FEMS Microbiol Lett 273:253–259PubMedCrossRefGoogle Scholar
  51. Wang Y, Wang G, Wang L, Xu X, Xia J, Huang X, Wu Y, Zhang C (2010) Isolation and identification of an endophytic fungus of Polygonatum cyrtonema and its antifungal metabolites. Wei sheng wu xue bao 50:1036–1043PubMedGoogle Scholar
  52. Wang LW, Xu BG, Wang JY, Su ZZ, Lin FC, Zhang CL, Kubicek CP (2012) Bioactive metabolites from Phoma species, an endophytic fungus from the Chinese medicinal plant Arisaema erubescens. Appl Microbiol Biotechnol 93:1231–1239PubMedCrossRefGoogle Scholar
  53. Wicklow DT, Roth S, Deyrup ST, Gloer JB (2005) A protective endophyte of maize: Acremonium zeae antibiotics inhibitory to Aspergillus flavus and Fusarium verticillioides. Mycol Res 109:610–618PubMedCrossRefGoogle Scholar
  54. Wu SH, Chen YW, Shao SC, Wang LD, Li ZY, Yang LY, Li SL, Huang R (2008) Ten-membered lactones from Phomopsis sp., an endophytic fungus of Azadirachta indica. J Nat Prod 71:731–734Google Scholar
  55. Xu Q, Wang J, Huang Y, Zheng Z, Song S, Zhang Y, Su W (2004) Metabolites from mangrove endophytic fungus Dothiorella sp. Acta Oceanol Sinica 23:541–547Google Scholar
  56. Zhang W, Krohn K, Draeger S, Schulz B (2008) Bioactive isocoumarins isolated from the endophytic fungus Microdochium bolleyi. J Nat Prod 71:1078–1081PubMedCrossRefGoogle Scholar
  57. Zhao J, Shan T, Huang Y, Liu X, Gao X, Wang M, Jiang W, Zhou L (2009) Chemical composition and in vitro antimicrobial activity of the volatile oils from Gliomastix murorum and Pichia guilliermondii, two endophytic fungi in Paris polyphylla var. yunnanensis. Nat Prod Commun 4:1491–1496PubMedGoogle Scholar
  58. Zheng CJ, Li L, Zou JP, Han T, Qin LP (2012) Identification of a quinazoline alkaloid produced by Penicillium vinaceum, an endophytic fungus from Crocus sativus. Pharm Biol 50:129–133PubMedCrossRefGoogle Scholar
  59. Zhu JW, Nagasawa H, Nagura F, Mohamad SB, Uto Y, Okura K, Hori H (2000) Elucidation of strict structural requirements of brefeldin A as an inducer of differentiation and apoptosis. Bioorg Med Chem 8:455–463PubMedCrossRefGoogle Scholar
  60. Zou WX, Meng JC, Lu H, Chen GX, Shi GX, Zhang TY, Tan RX (2000) Metabolites of Colletotrichum gloeosporioides, an endophytic fungus in Artemisia mongolica. J Nat Prod 63:1529–1530PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  1. 1.TERI UniversityNew DelhiIndia
  2. 2.The Energy and Resources Institute (TERI)New DelhiIndia

Personalised recommendations