Bioprocessing of Endophytes for Production of High-Value Biochemicals

  • Khwajah Mohinudeen
  • Karthik Devan
  • Smita SrivastavaEmail author


Metabolites produced by plants are of high significance owing to their therapeutic applications in humans. High demand for such natural plants has resulted in over-exploitation and endangered several species of plants. Endophytes reported to have the potential to produce similar high-value metabolites are often seen as alternatives for production of such metabolites. However, the product yield attenuation reported in endophytes with subsequent subculture prevents them from being commercially exploited. Yet reports on retrieval and enhancement in the yield of metabolites from endophytes under in vitro culture conditions continue to provide hope and interest of the scientific community in endophytic fermentation for commercial applications. In this chapter, we attempt to provide a consolidated view and latest developments in the area of endophyte bioprospecting and bioprocessing for large-scale production of various bioactive compounds including high-value phytochemicals and the possible role of plant-endophyte interaction on metabolite production by endophytes.


Endophytes Secondary metabolites Yield Bioprospecting Bioprocessing 



The authors would like to thank the Department of Science and Technology (DST), Government of India, New Delhi (EMR/2015/001418), for the financial assistance towards ongoing research projects.


  1. Aimi T, Taguchi H, Tanaka Y et al (2005) Agrobacterium tumefaciens-mediated genetic transformation of the white root rot ascomycete Rosellinia necatrix. Mycoscience 46:27–31. CrossRefGoogle Scholar
  2. Akinsanya MA, Goh JK, Lim SP, Ting ASY (2015) Diversity, antimicrobial and antioxidant activities of culturable bacterial endophyte communities in Aloe vera. FEMS Microbiol Lett 362:1–8. CrossRefGoogle Scholar
  3. Alvin A, Kalaitzis JA, Sasia B, Neilan BA (2016) Combined genetic and bioactivity-based prioritization leads to the isolation of an endophyte-derived antimycobacterial compound. J Appl Microbiol 120:1229–1239. CrossRefPubMedGoogle Scholar
  4. Alvin A, Miller KI, Neilan BA (2014) Exploring the potential of endophytes from medicinal plants as sources of antimycobacterial compounds. Microbiol Res 169:483–495. CrossRefPubMedGoogle Scholar
  5. Amna T, Amina M, Sharma PR et al (2012) Effect of precursors feeding and media manipulation on production of novel anticancer pro-drug camptothecin from endophytic fungus. Braz J Microbiol 43:1476–1489. CrossRefPubMedPubMedCentralGoogle Scholar
  6. Amna T, Khajuria RK, Puri SC et al (2006) Determination and quantification of camptothecin in an endophytic fungus by liquid chromatography – Positive mode electrospray ionization tandem mass spectrometry. Curr Sci 91:208–212Google Scholar
  7. Arivudainambi USE, Anand TD, Shanmugaiah V et al (2011) Novel bioactive metabolites producing endophytic fungus Colletotrichum gloeosporioides against multidrug-resistant Staphylococcus aureus. FEMS Immunol Med Microbiol 61:340–345. CrossRefPubMedGoogle Scholar
  8. Arnold AE, Mejia LC, Kyllo D et al (2003) Fungal endophytes limit pathogen damage in a tropical tree. Proc Natl Acad Sci 100:15649–15654. CrossRefPubMedGoogle Scholar
  9. Baldi A, Jain A, Gupta N et al (2008) Co-culture of arbuscular mycorrhiza-like fungi (Piriformospora indica and Sebacina vermifera) with plant cells of Linum album for enhanced production of podophyllotoxins: a first report. Biotechnol Lett 30:1671–1677. CrossRefPubMedGoogle Scholar
  10. Barrangou R, Fremaux C, Deveau H et al (2007) CRISPR provides acquired resistance against viruses in Prokaryotes. Science 315:1709–1712. CrossRefPubMedGoogle Scholar
  11. Béchamp A (1866) Du rôle de la craie dans les fermentations butyrique et lactique, et des organismes actuellement vivants qu’elle contient. C R Hebd Seances Acad Sci 63:451–456Google Scholar
  12. Beerling DJ, Osborne CP, Chaloner W (2001) Evolution of leaf form in land plants linked to atmospheric CO2 decline. Nature 410:352–354CrossRefGoogle Scholar
  13. Beijerinck MW (1888) Cultur des Bacillus radicicola aus den Knöllchen. Bot Ztg 46:740–750Google Scholar
  14. Besumbes O, Sauret-Gueto S, Phillips MA et al (2004) Metabolic engineering of isoprenoid biosynthesis in Arabidopsis for the production of taxadiene, the first committed precursor of taxol. Biotechnol Bioeng 88:168–175. CrossRefPubMedGoogle Scholar
  15. Betts MF, Tucker SL, Galadima N et al (2007) Development of a high throughput transformation system for insertional mutagenesis in Magnaporthe oryzae. Fungal Genet Biol 44:1035–1049. CrossRefPubMedGoogle Scholar
  16. Bhalkar BN, Bedekar PA, Patil SM et al (2015) Production of camptothecin using whey by an endophytic fungus: standardization using response surface methodology. RSC Adv 5:62828–62835. CrossRefGoogle Scholar
  17. Bhalkar BN, Patil SM, Govindwar SP (2016) Camptothecin production by mixed fermentation of two endophytic fungi from Nothapodytes nimmoniana. Fungal Biol 120:873–883. CrossRefPubMedGoogle Scholar
  18. Bölker M, Böhnert HU, Braun KH et al (1995) Tagging pathogenicity genes in Ustilago maydis by restriction enzyme-mediated integration (REMI). Mol Gen Genet 248:547–552. CrossRefPubMedGoogle Scholar
  19. Bundock P, den Dulk-Ras A, Beijersbergen A, Hooykaas PJ (1995) Trans-kingdom T-DNA transfer from Agrobacterium tumefaciens to Saccharomyces cerevisiae. EMBO J 14:3206–3214. CrossRefPubMedPubMedCentralGoogle Scholar
  20. Cao L, Huang J, Li J (2007) Fermentation conditions of Sinopodophyllum hexandrum endophytic fungus on production of podophyllotoxin. Food Ferment Ind 33:28–32Google Scholar
  21. Carroll GC (1991) Beyond pest deterrence. Alternative strategies and hidden costs of endophytic mutualisms in vascular plants. In: Andrews JH, Hirano SS (eds) Microbial ecology of leaves. Springer, New York, pp 358–375CrossRefGoogle Scholar
  22. Castillo UF, Strobel GA, Ford EJ et al (2002) Munumbicins, wide-spectrum antibiotics produced by Streptomyces NRRL 30562, endophytic on Kennedia nigriscans. Microbiology 148:2675–2685. CrossRefPubMedGoogle Scholar
  23. Chaichanan J, Wiyakrutta S, Pongtharangkul T et al (2014) Optimization of zofimarin production by an endophytic fungus, Xylaria sp. Acra L38. Braz J Microbiol 45:287–293. CrossRefPubMedPubMedCentralGoogle Scholar
  24. Chandra S (2012) Endophytic fungi: novel sources of anticancer lead molecules. Appl Microbiol Biotechnol 95:47–59CrossRefGoogle Scholar
  25. Chen J, Lai Y, Wang L et al (2017) CRISPR/Cas9-mediated efficient genome editing via blastospore-based transformation in entomopathogenic fungus Beauveria bassiana. Sci Rep 8:1–10. CrossRefGoogle Scholar
  26. Chithra S, Jasim B, Anisha C et al (2014) LC-MS/MS based identification of piperine production by endophytic Mycosphaerella sp. PF13 from Piper nigrum. Appl Biochem Biotechnol 173:30–35. CrossRefPubMedGoogle Scholar
  27. Chowdhary K, Kaushik N (2015) Fungal endophyte diversity and bioactivity in the Indian medicinal plant Ocimum sanctum Linn. PLoS One 10:1–25. CrossRefGoogle Scholar
  28. Collado J, Platas G, Gonzalez I, Pelaez F (1999) Geographical and seasonal influences on the distribution of fungal endophytes in Quercus ilex. New Phytol 144:525–532CrossRefGoogle Scholar
  29. Compant S, Sessitsch A, Mathieu F (2012) The 125th anniversary of the first postulation of the soil origin of endophytic bacteria – a tribute to M.L.V. Galippe. Plant Soil 356:299–301. CrossRefGoogle Scholar
  30. Cui Q, Lewis IA, Hegeman AD et al (2008) Metabolite identification via the Madison Metabolomics consortium database. Nat Biotechnol 26:162–164. CrossRefPubMedGoogle Scholar
  31. Dar RA, Saba I, Shahnawaz M et al (2017) Antimicrobial potential of fungal endophytes from selected high value medicinal plants of the Kashmir valley – India, vol 6, pp 307–310Google Scholar
  32. Das A, Rahman MI, Ferdous AS et al (2017) An endophytic Basidiomycete, Grammothele lineata, isolated from Corchorus olitorius, produces paclitaxel that shows cytotoxicity. PLoS One 12:1–17. CrossRefGoogle Scholar
  33. Deng BW, Liu KH, Chen WQ et al (2009) Fusarium solani, Tax-3, a new endophytic taxol-producing fungus from Taxus chinensis. World J Microbiol Biotechnol 25:139–143. CrossRefGoogle Scholar
  34. Ding C, Wang Q-B, Guo S, Wang Z (2017) The improvement of bioactive secondary metabolites accumulation in Rumex gmelini Turcz through co-culture with endophytic fungi. Braz J Microbiol:1–8. CrossRefGoogle Scholar
  35. Doudna JA, Charpentier E (2014) The new frontier of genome engineering with CRISPR-Cas9. Science 346:1258096. CrossRefPubMedGoogle Scholar
  36. Dubey D, Rath S, Sahu MC et al (2012) Antimicrobials of plant origin against TB and other infections and economics of plant drugs -Introspection. Indian J Tradit Knowl 11:225–233Google Scholar
  37. Dushenkov V (2016) Biodiversity of medicinal plants in the highlands: problems and perspectives. In: Yakubova MM (ed) The state of biological resources in mountain regions in relation to climate change. Donish, Khorog, pp 191–192Google Scholar
  38. Eyberger AL, Dondapati R, Porter JR (2006) Endophyte fungal isolates from Podophyllum peltatum produce podophyllotoxin. J Nat Prod 69:1121–1124. CrossRefPubMedGoogle Scholar
  39. Ezra D, Castillo UF, Strobel GA et al (2004) Coronamycins, peptide antibiotics produced by a verticillate Streptomyces sp. (MSU-2110) endophytic on Monstera sp. Microbiology 150:785–793. CrossRefPubMedGoogle Scholar
  40. Fisher PJ, Petrini O, Sutton BC (1993) A comparative study of fungal endophytes in leaves, xylem and bark of Eucalyptus in Australia and England. Sydowia 45:338–345. CrossRefGoogle Scholar
  41. Frank B (1885) Ueber die auf Wurzelsymbiose beruhende Ernahrung gewisser Baume durch unterirdische Pilze. Ber dt Bot Ges 3:128–145Google Scholar
  42. Freire-Moran L, Aronsson B, Manz C et al (2011) Critical shortage of new antibiotics in development against multidrug-resistant bacteria – Time to react is now. Drug Resist Updat 14:118–124. CrossRefPubMedGoogle Scholar
  43. Fulzele DP, Satdive RK (2005) Comparison of techniques for the extraction of the anti-cancer drug camptothecin from Nothapodytes foetida. J Chromatogr Sci 1063:9–13. CrossRefGoogle Scholar
  44. Galippe V (1887) Note sur la présence de micro-organismes dans les tissus végétaux. Comptes Rendus Hebd des Séances Mémoires la Société Biol des ses. Fil Assoc 39:410–416Google Scholar
  45. Gangadevi V, Muthumary J (2008) A simple and rapid method for the determination of taxol produced by fungal endophytes from medicinal plants using high performance thin layer chromatography. Chin J Chromatogr 26:50–55. CrossRefGoogle Scholar
  46. Gao Y, Yin H, Sun Y et al (2008) Mutagenesis of a Berberine-Producing Endophytic Fungus. J Fungal Res 4:6Google Scholar
  47. Gaosheng H, Jingming J (2012) Production of useful secondary metabolites through regulation of biosynthetic pathway in cell and tissue suspension culture of medicinal plants. Recent Adv Plant Vitr Cult 11:197–210. doi: 40188Google Scholar
  48. Gohain A, Gogoi A, Debnath R et al (2015) Antimicrobial biosynthetic potential and genetic diversity of endophytic actinomycetes associated with medicinal plants. FEMS Microbiol Lett 362:1–10. CrossRefGoogle Scholar
  49. Golinska P, Wypij M, Agarkar G et al (2015) Endophytic actinobacteria of medicinal plants: diversity and bioactivity. Antonie van Leeuwenhoek. Int J Gen Mol Microbiol 108:267–289. CrossRefGoogle Scholar
  50. Grobe N, Lamshöft M, Orth RG et al (2010) Urinary excretion of morphine and biosynthetic precursors in mice. Proc Natl Acad Sci U S A 107:8147–8152. CrossRefPubMedPubMedCentralGoogle Scholar
  51. Guimarães DO, Borges WS, Kawano CY et al (2008) Biological activities from extracts of endophytic fungi isolated from Viguiera arenaria and Tithonia diversifolia. FEMS Immunol Med Microbiol 52:134–144. CrossRefPubMedGoogle Scholar
  52. Guo B, Li H, Zhang L (1998) Isolation of an fungus producing Vinblastine. J Yunnan Univ (Nat Sci Edit) 20:214–215Google Scholar
  53. Guo LD, Hyde KD, Liew ECY (2000) Identification of endophytic fungi from Livistona chinensis based on morphology and rDNA sequences. New Phytol 147:617–630. doi: undefinedCrossRefGoogle Scholar
  54. Gurudatt PS, Priti V, Shweta S et al (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 98:1006–1010Google Scholar
  55. Hata K, Sone K (2008) Isolation of endophytes from leaves of Neolitsea sericea in broadleaf and conifer stands. Mycoscience 49:229–232. CrossRefGoogle Scholar
  56. Hernández C, Milagres AMF, Vázquez-Marrufo G et al (2018) An ascomycota coculture in batch bioreactor is better than polycultures for cellulase production. Folia Microbiol. CrossRefGoogle Scholar
  57. Hidayat I, Radiastuti N, Rahayu G et al (2015) Three Quinine – and Cinchonidine – producing Fusarium species from Indonesia. Curr Res Environ Appl Mycol 6:20–34. CrossRefGoogle Scholar
  58. Holton RA, Kim HB, Somoza C et al (1994a) First total synthesis of taxol. 2. Completion of the C and D rings. J Am Chem Soc 116:1599–1600. CrossRefGoogle Scholar
  59. Holton RA, Somoza C, Kim HB et al (1994b) First total synthesis of taxol. 1. Functionalization of the B ring. J Am Chem Soc 116:1597–1598. CrossRefGoogle Scholar
  60. Howat S, Park B, Oh IS et al (2014) Paclitaxel: biosynthesis, production and future prospects. New Biotechnol 31:242–245. CrossRefGoogle Scholar
  61. Howitz KT, Sinclair DA (2008) Xenohormesis: sensing the chemical Cues of other species. Cell 133:387–391. CrossRefPubMedPubMedCentralGoogle Scholar
  62. Huang Y, Wang J, Li G et al (2001) Antitumor and antifungal activities in endophytic fungi isolated from pharmaceutical plants Taxus mairei, Cephalataxus fortunei and Torreya grandis. FEMS Immunol Med Microbiol 31:163–167. CrossRefPubMedGoogle Scholar
  63. Jianfeng W, Huaying L, Yaojian H et al (1999) A taxol-producing endophytic fungus isolated from Taxus mairei and it’s antitumor activity. J Xiamen Univ Sci 38:485–487Google Scholar
  64. Ju Z, Wang J, Pan SL (2009) Isolation and preliminary identification of the endophytic fungi which produce Hupzine A from four species in Hupziaceae and determination of Huperzine A by HPLC. Fudan Univ J Med Sci 4:17Google Scholar
  65. Kai G, Wu C, Gen L et al (2015) Biosynthesis and biotechnological production of anti-cancer drug Camptothecin. Phytochem Rev 14:525–539. CrossRefGoogle Scholar
  66. Karwasara VS, Dixit VK (2013) Culture medium optimization for camptothecin production in cell suspension cultures of Nothapodytes nimmoniana. (J Grah) Mabberley Plant Biotechnol Rep 7:357–369. CrossRefGoogle Scholar
  67. Kloepper JW, McInroy JA, Liu K, Hu CH (2013) Symptoms of Fern distortion syndrome resulting from inoculation with opportunistic endophytic fluorescent Pseudomonas spp. PLoS One 8:e58531. CrossRefPubMedPubMedCentralGoogle Scholar
  68. Koeller KM, Wong CH (2001) Enzymes for chemical synthesis. Nature 409:232–240. CrossRefPubMedGoogle Scholar
  69. Korkama-Rajala T, Müller MM, Pennanen T (2008) Decomposition and fungi of needle litter from slow- and fast-growing Norway spruce (Picea abies) clones. Microb Ecol 56:76–89. CrossRefPubMedGoogle Scholar
  70. Korkina LG (2007) Phenylpropanoids as naturally occurring antioxidants: from plant defense to human health. Cell Mol Biol 53:15–25. CrossRefPubMedGoogle Scholar
  71. Kour A, Shawl AS, Rehman S et al (2008) Isolation and identification of an endophytic strain of Fusarium oxysporum producing podophyllotoxin from Juniperus recurva. World J Microbiol Biotechnol 24:1115–1121. CrossRefGoogle Scholar
  72. Krings M, Taylor TN, Dotzler N (2012) Fungal endophytes as a driving force in land plant evolution: evidence from the fossil record. In: Southworth D (ed) Biocomplexity of plant–fungal interactions. Wiley, New York, pp 5–28CrossRefGoogle Scholar
  73. Kumar A, Patil D, Rajamohanan PR, Ahmad A (2013) Isolation, purification and characterization of vinblastine and vincristine from endophytic fungus Fusarium oxysporum isolated from Catharanthus roseus. PLoS One 8:e71805. CrossRefPubMedPubMedCentralGoogle Scholar
  74. Kumara PM, Soujanya KN, Ravikanth G et al (2014) Rohitukine, a chromone alkaloid and a precursor of flavopiridol, is produced by endophytic fungi isolated from Dysoxylum binectariferum Hook.f and Amoora rohituka (Roxb).Wight & Arn. Phytomedicine 21:541–546. CrossRefPubMedGoogle Scholar
  75. Kumaran RS, Jung H, Kim HJ (2011) In vitro screening of taxol, an anticancer drug produced by the fungus, Colletotrichum capsici. Eng Life Sci 11:264–271. CrossRefGoogle Scholar
  76. Kumaran RS, Kim HJ, Hur BK (2010) Taxol promising fungal endophyte, Pestalotiopsis species isolated from Taxus cuspidata. J Biosci Bioeng 110:541–546. CrossRefPubMedGoogle Scholar
  77. Kusari S, Hertweck C, Spiteller M (2012a) Chemical ecology of endophytic fungi: origins of secondary metabolites. Chem Biol 19:792–798. CrossRefPubMedGoogle Scholar
  78. Kusari S, Lamshöft M, Spiteller M (2009a) Aspergillus fumigatus Fresenius, an endophytic fungus from Juniperus communis L. Horstmann as a novel source of the anticancer pro-drug deoxypodophyllotoxin. J Appl Microbiol 107:1019–1030CrossRefGoogle Scholar
  79. Kusari S, Lamshöft M, Zühlke S, Spiteller M (2008) An endophytic fungus from Hypericum perforatum that produces hypericin. J Nat Prod 71:159–162CrossRefGoogle Scholar
  80. Kusari S, Verma VC, Lamshoeft M, Spiteller M (2012b) An endophytic fungus from Azadirachta indica A. Juss. that produces azadirachtin. World J Microbiol Biotechnol 28:1287–1294. CrossRefPubMedGoogle Scholar
  81. Kusari S, Zühlke S, Spiteller M (2009b) An endophytic fungus from Camptotheca acuminata that produces camptothecin and analogues. J Nat Prod 72:2–7. CrossRefPubMedGoogle Scholar
  82. Li JY, Sidhu RS, Ford EJ et al (1998) The induction of taxol production in the endophytic fungus – Periconia sp from Torreya grandifolia. J Ind Microbiol Biotechnol 20:259–264. CrossRefGoogle Scholar
  83. Li W, Zhou J, Lin Z, Hu Z (2007) Study on fermentation condition for production of huperzine A from endophytic fungus 2F09P03B of Huperzia serrata. Chin Med Biotechnol 2:254–259Google Scholar
  84. Li Y-C, Tao W-Y, 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. CrossRefPubMedGoogle Scholar
  85. Linden JC (2006) Secondary products from plant tissue culture. Encycl Life Support Syst (UNESCO-EOLSS) Biotechnol 4:1–9Google Scholar
  86. Link HF (1809) Observationes in ordines plantarum naturales. Die Gesellschaft naturforschender Freunde zu Berlin: Magazin für die neuesten Entdeckungen in der gesammten Naturkunde 3:33Google Scholar
  87. Liu K, Ding X, Deng B, Chen W (2010) 10-Hydroxycamptothecin produced by a new endophytic Xylaria sp., M20, from Camptotheca acuminata. Biotechnol Lett 32:689–693. CrossRefPubMedGoogle Scholar
  88. Liu K, Ding X, Deng B, Chen W (2009) Isolation and characterization of endophytic taxol-producing fungi from Taxus chinensis. J Ind Microbiol Biotechnol 36:1171–1177. CrossRefPubMedGoogle Scholar
  89. Liu L, Wei YM, Zhou XW et al (2013) Agrobacterium tumefaciens-mediated genetic transformation of the Taxol-producing endophytic fungus Ozonium sp EFY21. Genet Mol Res 12:2913–2922. CrossRefPubMedGoogle Scholar
  90. Liu Z, Carpenter SB, Bourgeois WJ et al (1998) Variations in the secondary metabolite camptothecin in relation to tissue age and season in Camptotheca acuminata. Tree Physiol 18:265–270. CrossRefPubMedGoogle Scholar
  91. Long DM, Smidansky ED, Archer AJ, Strobel GA (1998) In vivo addition of telomeric repeats to foreign DNA generates extrachromosomal DNAs in the taxol-producing fungus Pestalotiopsis microspora. Fungal Genet Biol 24:335–344. CrossRefPubMedGoogle Scholar
  92. Machavariani NG, Ivankova TD, Sineva ON, Terekhova LP (2014) Isolation of endophytic actinomycetes from medicinal plants of the Moscow region. Russia World Appl Sci J 30:1599–1604Google Scholar
  93. Maehara S, Simanjuntak P, Kitamura C et al (2011) Cinchona alkaloids are also produced by an endophytic filamentous fungus living in cinchona plant. Chem Pharm Bull (Tokyo) 59:1073–1074. CrossRefGoogle Scholar
  94. Maehara S, Simanjuntak P, Maetani Y et al (2013) Ability of endophytic filamentous fungi associated with Cinchona ledgeriana to produce Cinchona alkaloids. J Nat Med 67:421–423. CrossRefPubMedGoogle Scholar
  95. Martinez-Klimova E, Rodríguez-Peña K, Sánchez S (2017) Endophytes as sources of antibiotics. Biochem Pharmacol 134:1–17. CrossRefPubMedGoogle Scholar
  96. Melo IS, Santos SN, Rosa LH et al (2014) Isolation and biological activities of an endophytic Mortierella alpina strain from the Antarctic moss Schistidium antarctici. Extremophiles 18:15–23. CrossRefPubMedGoogle Scholar
  97. Michielse CB, Arentshorst M, Ram AFJ, Van Den Hondel CAMJJ (2005) Agrobacterium-mediated transformation leads to improved gene replacement efficiency in Aspergillus awamori. Fungal Genet Biol 42:9–19. CrossRefPubMedGoogle Scholar
  98. Miller KI, Qing C, Sze DMY et al (2012a) culturable endophytes of medicinal plants and the genetic basis for their bioactivity. Microb Ecol 64:431–449. CrossRefPubMedGoogle Scholar
  99. Miller KI, Qing C, Sze DMY, Neilan BA (2012b) Investigation of the biosynthetic potential of endophytes in traditional Chinese anticancer herbs. PLoS One 7:1–12. CrossRefGoogle Scholar
  100. Milne SB, Mathews TP, Myers DS et al (2013) Sum of the parts: mass spectrometry-based metabolomics. Biochemistry 52:3829–3840. CrossRefPubMedPubMedCentralGoogle Scholar
  101. Mousa WK, Schwan A, Davidson J et al (2015) An endophytic fungus isolated from finger millet (Eleusine coracana) produces anti-fungal natural products. Front Microbiol 6:1157. CrossRefPubMedPubMedCentralGoogle Scholar
  102. Müller P, Döring M (2009) Isothermal DNA amplification facilitates the identification of a broad spectrum of bacteria, fungi and protozoa in Eleutherococcus sp. plant tissue cultures. Plant Cell Tissue Organ Cult 98:35–45. CrossRefGoogle Scholar
  103. Nadeem M, Ram M, Alam P et al (2012) Fusarium solani, P1, a new endophytic podophyllotoxin-producing fungus from roots of Podophyllum hexandrum. Afr J Microbiol Res 6:2493–2499. CrossRefGoogle Scholar
  104. Narayani M, Srivastava S (2017) Elicitation: a stimulation of stress in in vitro plant cell/tissue cultures for enhancement of secondary metabolite production. Phytochem Rev 16:1227–1252. CrossRefGoogle Scholar
  105. Newman DJ, Cragg GM (2007) Natural products as sources of new drugs over the last 25 years. J Nat Prod 70:461–477. CrossRefPubMedGoogle Scholar
  106. Ola ARB, Thomy D, Lai D et al (2013) Inducing secondary metabolite production by the endophytic fungus Fusarium tricinctum through coculture with Bacillus subtilis. J Nat Prod 76:2094–2099. CrossRefPubMedGoogle Scholar
  107. Pai SR, Pawar NV, Nimbalkar MS et al (2013) Seasonal variation in content of camptothecin from the bark of Nothapodytes nimmoniana (Grah.) Mabb., using HPLC analysis. Pharm Res 5:219–223. CrossRefGoogle Scholar
  108. Palem PPC, Kuriakose GC, Jayabaskaran C (2015) An endophytic fungus, talaromyces radicus, isolated from catharanthus roseus, produces vincristine and vinblastine, which induce apoptotic cell death. PLoS One 10:e0144476. CrossRefPubMedPubMedCentralGoogle Scholar
  109. Pan X-W, Xu H-H, Liu X et al (2004) Improvement of growth and camptothecin yield by altering nitrogen source supply in cell suspension cultures of Camptotheca acuminata. Biotechnol Lett 26:1745–1748. CrossRefPubMedGoogle Scholar
  110. Parsa S, Ortiz V, Vega FE (2013) Establishing fungal entomopathogens as endophytes: towards endophytic biological control. J Vis Exp 1(5).
  111. Petrini O (1991) Fungal endophytes of tree leaves. In: Andrews JH, Hirano SS (eds) Microbial ecology of leaves. Springer, New York, pp 179–197CrossRefGoogle Scholar
  112. Prakash CP, Thirumalai E, Govinda Rajulu MB et al (2015) Ecology and diversity of leaf litter fungi during early-stage decomposition in a seasonally dry tropical forest. Fungal Ecol 17:103–113. CrossRefGoogle Scholar
  113. Pu X, Qu X, Chen F et al (2013) Camptothecin-producing endophytic fungus Trichoderma atroviride LY357: isolation, identification, and fermentation conditions optimization for camptothecin production. Appl Microbiol Biotechnol 97:9365–9375. CrossRefPubMedGoogle Scholar
  114. Puri SC, Nazir A, Chawla R et al (2006) The endophytic fungus Trametes hirsuta as a novel alternative source of podophyllotoxin and related aryl tetralin lignans. J Biotechnol 122:494–510. CrossRefPubMedGoogle Scholar
  115. Puri SG, Verma V, Amna T et al (2005) An endophytic fungus from Nothapodytes foetida that produces camptothecin. J Nat Prod 68:1717–1719. CrossRefPubMedGoogle Scholar
  116. Qiao W, Ling F, Yu L et al (2017) Enhancing taxol production in a novel endophytic fungus, Aspergillus aculeatinus Tax-6, isolated from Taxus chinensis var. mairei. Fungal Biol 121:1037–1044. CrossRefPubMedGoogle Scholar
  117. Rabha AJ, Sharma GD, Naglot A, Gogoi HK (2015) GC-MS analysis of secondary metabolites of endophytic Colletotrichum Gloeosporioides isolated from Camellia Sinensis (L) O. Kuntze. Int J Innov Res Sci Eng 3:373–379Google Scholar
  118. Ramesha BT, Amna T, Ravikanth G et al (2008) Prospecting for camptothecins from Nothapodytes nimmoniana in the Western Ghats, South India: identification of high-yielding sources of camptothecin and new families of camptothecins. J Chromatogr Sci 46:362–368CrossRefGoogle Scholar
  119. Rani R, Sharma D, Chaturvedi M, Parkash Yadav J (2017) Antibacterial Activity of Twenty Different Endophytic Fungi Isolated from Calotropis procera and Time Kill Assay. Clin Microbiol Open Access 6(2).
  120. Raven J, Edwards D (2001) Roots: evolutionary origins and biogeochemical significance. J Exp Bot 52:381–401. CrossRefPubMedGoogle Scholar
  121. Ray S, Singh V, Bisen K, Keswani C, Singh S, Singh HB (2017) Endophytomicrobiont: a multifaceted beneficial interaction. In: Singh HB, Sarma BK, Keswani C (eds) Advances in PGPR Research. CABI, Wallingford, Oxfordshire, pp 218–233.
  122. Rehman S, Shawl AS, Kour A et al (2008) An endophytic Neurospora sp. from Nothapodytes foetida producing camptothecin. Appl Biochem Microbiol 44:203–209. CrossRefGoogle Scholar
  123. Renpeng T, Qiao Y, Guoling Z et al (2006) Taxonomic study on a taxol producing fungus isolated from bark of Taxus chinensis var. mairei. J Wuhan Bot Res 24:541–545Google Scholar
  124. Rodriguez RJ, White JF, Arnold a E, Redman RS (2009) Fungal endophytes: diversity and functional roles. New Phytol 182:314–330. CrossRefPubMedGoogle Scholar
  125. Santoyo G, Moreno-Hagelsieb G, del Carmen Orozco-Mosqueda M, Glick BR (2016) Plant growth-promoting bacterial endophytes. Microbiol Res 183:92–99. CrossRefPubMedGoogle Scholar
  126. Sathiyabama M, Parthasarathy R (2017) Withanolide production by fungal endophyte isolated from Withania somnifera. Nat Prod Res 6419:1–5. CrossRefGoogle Scholar
  127. Schauer N, Steinhauser D, Strelkov S et al (2005) GC-MS libraries for the rapid identification of metabolites in complex biological samples. FEBS Lett 579:1332–1337. CrossRefPubMedGoogle Scholar
  128. Schiestl RH, Petes TD (1991) Integration of DNA fragments by illegitimate recombination in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 88:7585–7589. CrossRefPubMedPubMedCentralGoogle Scholar
  129. Shweta S, Bindu JH, Raghu J et al (2013) Isolation of endophytic bacteria producing the anti-cancer alkaloid camptothecin from Miquelia dentata Bedd. (Icacinaceae). Phytomedicine 20:913–917. CrossRefPubMedGoogle Scholar
  130. Shweta S, Zuehlke S, Ramesha BT et al (2010) Endophytic fungal strains of Fusarium solani, from Apodytes dimidiata E. Mey. ex Arn (Icacinaceae) produce camptothecin, 10-hydroxycamptothecin and 9-methoxycamptothecin. Phytochemistry 71:117–122. CrossRefPubMedPubMedCentralGoogle Scholar
  131. Singh HB, Sarma BK, Keswani C (eds) (2016) Agriculturally important microorganisms: commercialization and regulatory requirements in Asia. Springer, SingaporeGoogle Scholar
  132. Singh HB, Sarma BK, Keswani C (eds) (2017) Advances in PGPR. CABI, Wallingford, OxfordshireGoogle Scholar
  133. Smith CA (2005) METLIN—A metabolite mass spectral database. Ther Drug Monit 27:747–751. CrossRefPubMedGoogle Scholar
  134. Soliman SSM, Mosa KA, El-Keblawy AA, Husseiny MI (2017) Exogenous and endogenous increase in fungal GGPP increased fungal Taxol production. Appl Microbiol Biotechnol 101:7523–7533. CrossRefPubMedGoogle Scholar
  135. Soliman SSM, Raizada MN (2013) Interactions between co-habitating fungi elicit synthesis of Taxol from an endophytic fungus in host Taxus plants. Front Microbiol 4:1–14. CrossRefGoogle Scholar
  136. Somjaipeng S, Medina A, Magan N (2016) Environmental stress and elicitors enhance taxol production by endophytic strains of Paraconiothyrium variabile and Epicoccum nigrum. Enzym Microb Technol 90:69–75. CrossRefGoogle Scholar
  137. Soujanya KN, Siva R, Mohana Kumara P et al (2017) Camptothecin-producing endophytic bacteria from Pyrenacantha volubilis Hook. (Icacinaceae): a possible role of a plasmid in the production of camptothecin. Phytomedicine 36:160–167. CrossRefPubMedGoogle Scholar
  138. Stierle A, Strobel G, Stierle D (1993) Taxol and taxane production by Taxomyces andreanae, an endophytic fungus of Pacific yew. Science 260:214–216. CrossRefPubMedPubMedCentralGoogle Scholar
  139. Stoppacher N, Kluger B, Zeilinger S et al (2010) Identification and profiling of volatile metabolites of the biocontrol fungus Trichoderma atroviride by HS-SPME-GC-MS. J Microbiol Methods 81:187–193. CrossRefPubMedGoogle Scholar
  140. Sun D, Ran X, Wang J (2008) Isolation and identification of a taxol-producing endophytic fungus from Podocarpus. Acta Microbiol Sin 48:589–595Google Scholar
  141. Tanvir R, Sajid I, Hasnain S et al (2016) Rare actinomycetes Nocardia caishijiensis and Pseudonocardia carboxydivorans as endophytes, their bioactivity and metabolites evaluation. Microbiol Res 185:22–35. CrossRefPubMedGoogle Scholar
  142. Taylor L (2005) The healing power of rainforest herbs. A guide to understanding and using herbal medicinals. Square One Publishers, New YorkGoogle Scholar
  143. Taylor TN, Taylor EL (1993) The biology and evolution of fossil plants, 1st edn. Prentice Hall, Englewood CliffsGoogle Scholar
  144. Thammajaruk N, Sriubolmas N, Israngkul D et al (2011) Optimization of culture conditions for mycoepoxydiene production by Phomopsis sp. Hant25. J Ind Microbiol Biotechnol 38:679–685. CrossRefPubMedGoogle Scholar
  145. Thiry M, Cingolani D (2002) Optimizing scale-up fermentation processes. Trends Biotechnol 20:103–105CrossRefGoogle Scholar
  146. Tian R, Yang Q, Zhou G et al (2005) Taxonomic study on a taxol producing fungus isolated from bark of Taxus chinensis var. mairei. Wuhan Bot Res 24:541–545Google Scholar
  147. Trémouillaux-Guiller J, Rohr T, Rohr R, Huss VAR (2002) Discovery of an endophytic alga in Ginkgo biloba. Am J Bot 89:727–733. CrossRefPubMedGoogle Scholar
  148. Unterseher M, Schnittler M (2009) Dilution-to-extinction cultivation of leaf-inhabiting endophytic fungi in beech (Fagus sylvatica L.) – Different cultivation techniques influence fungal biodiversity assessment. Mycol Res 113:645–654. CrossRefPubMedGoogle Scholar
  149. Uzor PF, Osadebe PO, Nwodo NJ (2017) Antidiabetic activity of extract and compounds from an endophytic fungus Nigrospora oryzae. Drug Res 67:308–311. CrossRefGoogle Scholar
  150. van Hengel AJ, Harkes MP, Wichers HJ et al (1992) Characterization of callus formation and camptothecin production by cell lines of Camptotheca acuminata. Plant Cell Tissue Organ Cult 28:11–18. CrossRefGoogle Scholar
  151. Vance NC, Kelsey RG, Sabin TE (1994) Seasonal and tissue variation in taxane concentrations of Taxus brevifolia. Phytochemistry 36:1241–1244. CrossRefPubMedGoogle Scholar
  152. Vasanthakumari MM, Jadhav SS, Sachin N et al (2015) Restoration of camptothecin production in attenuated endophytic fungus on re-inoculation into host plant and treatment with DNA methyltransferase inhibitor. World J Microbiol Biotechnol 31:1629–1639. CrossRefPubMedGoogle Scholar
  153. Vasundhara M, Kumar A, Reddy MS (2016) Molecular approaches to screen bioactive compounds from endophytic fungi. Front Microbiol 7:1–12. CrossRefGoogle Scholar
  154. Venugopalan A, Potunuru UR, Dixit M, Srivastava S (2016) Effect of fermentation parameters, elicitors and precursors on camptothecin production from the endophyte Fusarium solani. Bioresour Technol 206:104–111. CrossRefPubMedPubMedCentralGoogle Scholar
  155. Venugopalan A, Srivastava S (2015) Endophytes as in vitro production platforms of high value plant secondary metabolites. Biotechnol Adv 33:873–887. CrossRefPubMedGoogle Scholar
  156. Verma VC, Gond SK, Kumar A et al (2009) Endophytic actinomycetes from Azadirachta indica A. Juss.: isolation, diversity, and anti-microbial activity. Microb Ecol 57:749–756. CrossRefPubMedGoogle Scholar
  157. Voriskova J, Baldrian P (2013) Fungal community on decomposing leaf litter undergoes rapid successional changes. ISME J 7:477–486. CrossRefPubMedGoogle Scholar
  158. Wall ME, Wani MC, Cook CE et al (1966) Plant Antitumor Agents. I. the isolation and structure of camptothecin, a Novel Alkaloidal Leukemia and Tumor Inhibitor from Camptotheca acuminata. J Am Chem Soc 88:3888–3890. CrossRefGoogle Scholar
  159. Wang J, Li G, Lu H et al (2000) Taxol from Tubercularia sp. strain TF5, an endophytic fungus of Taxus mairei. FEMS Microbiol Lett 193:249–253. CrossRefPubMedGoogle Scholar
  160. Wang L, Qiu P, Long XF et al (2016) Comparative analysis of chemical constituents, antimicrobial and antioxidant activities of ethylacetate extracts of Polygonum cuspidatum and its endophytic actinomycete, Streptomyces sp. A0916. Chin J Nat Med 14:117–123. CrossRefPubMedGoogle Scholar
  161. Wang Q, Fu Y, Gao J et al (2007a) Preliminary isolation and screen of endophytic fungi from Melia azedarach L. Acta Agric Boreali-Occiden Sin 16:224–227Google Scholar
  162. Wang Y, Guo B, Miao Z, Tang K (2007b) Transformation of taxol-producing endophytic fungi by restriction enzyme-mediated integration (REMI). FEMS Microbiol Lett 273:253–259. CrossRefPubMedGoogle Scholar
  163. Wani MC, Taylor HL, Wall ME et al (1971) Plant Antitumor Agents.VI.the isolation and structure of Taxol, a Novel Antileukemic and Antitumor agent from Taxus brevifolia. J Am Chem Soc 93:2325–2327. CrossRefPubMedGoogle Scholar
  164. Wei Y, Liu L, Zhou X et al (2012) Engineering taxol biosynthetic pathway for improving taxol yield in taxol-producing endophytic fungus EFY-21 (Ozonium sp.). Afr J Biotechnol 11:9094–9101. CrossRefGoogle Scholar
  165. Wei Y, Zhou X, Liu L et al (2010) An efficient transformation system of taxol-producing endophytic fungus EFY-21 (Ozonium sp.). Afr J Biotechnol 9:1726–1733CrossRefGoogle Scholar
  166. Wishart DS, Knox C, Guo AC et al (2009) HMDB: a knowledgebase for the human metabolome. Nucleic Acids Res 37:603–610. CrossRefGoogle Scholar
  167. Wolfender JL, Ndjoko K, Hostettmann K (2001) The potential of LC-NMR in phytochemical analysis. Phytochem Anal 12:2–22.<2::AID-PCA552>3.0.CO;2-K CrossRefPubMedGoogle Scholar
  168. Xiao-dong C, Jia-ru L, Li-gang Z et al (2007) Determination of diosgenin content of the endophytic fungi from Paris polyphylla var. yunnanensis by using an optimum ELISA. Nat Prod Res Dev 19:1020–1023Google Scholar
  169. Xu LJ, Liu YS, Zhou LG, Wu JY (2010) Optimization of a liquid medium for beauvericin production in Fusarium redolens dzf2 mycelial culture. Biotechnol Bioprocess Eng 15:460–466. CrossRefGoogle Scholar
  170. Yang X, Guo S, Zhang L, Shao H (2003) Select of producing podophyllotoxin endophytic fungi from podophyllin plant. Nat Prod Res Dev 15:419–422Google Scholar
  171. 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 Herb drugs 35:79–81Google Scholar
  172. Yang Y, Zhao H, R a B et al (2014) Genome sequencing and analysis of the paclitaxel-producing endophytic fungus Penicillium aurantiogriseum NRRL 62431. BMC Genomics 15:69. CrossRefPubMedPubMedCentralGoogle Scholar
  173. Yin H, Chen J (2011) The fermentation conditions of a sipeimine producing endophytic fungus isolated from Fritillaria ussuriensis. J Northwest Univ (Natural Sci Ed) 2:18Google Scholar
  174. Yin H, Sun YH (2011) Vincamine-producing endophytic fungus isolated from Vinca minor. Phytomedicine 18:802–805. CrossRefPubMedGoogle Scholar
  175. Yu S, Huang QQ, Luo Y, Lu W (2012) Total synthesis of camptothecin and SN-38. J Org Chem 77:713–717. CrossRefPubMedGoogle Scholar
  176. Yue W, Ming Q, Lin B et al (2016) Medicinal plant cell suspension cultures: pharmaceutical applications and high-yielding strategies for the desired secondary metabolites. Crit Rev Biotechnol 36:215–232. CrossRefPubMedGoogle Scholar
  177. Zhang L, Guo B, Li H et al (2000) Preliminary study on the isolation of endophytic fungus of Catharanthus roseus and its fermentation to produce products of therapeutic value. Chin Tradit Herb drugs 31:805–807Google Scholar
  178. Zhang P, Zhou PP, Yu LJ (2009) An endophytic taxol-producing fungus from taxus media, cladosporium cladosporioides MD2. Curr Microbiol 59:227–232. CrossRefPubMedGoogle Scholar
  179. Zhao J, Zhou L, Wang J, Shan T (2010) Endophytic fungi for producing bioactive compounds originally from their host plants. Curr Res Technol Educ Top Appl Microbiol Microb Biotechnol 1:567–576. CrossRefGoogle Scholar
  180. Zheng Y, Xue QY, Xu LL et al (2011) A screening strategy of fungal biocontrol agents towards Verticillium wilt of cotton. Biol Control 56:209–216. CrossRefGoogle Scholar
  181. Zhou L, Cao X, Yang C et al (2004) Endophytic fungi of Paris polyphylla var. yunnanensis and steroid analysis in the fungi. Nat Prod Res Dev 16:198–200Google Scholar
  182. Zhou S, Yang F, Lan S et al (2009) Huperzine A producing conditions from endophytic fungus in SHB Huperzia serrata. J Microbiol 3:32–36Google Scholar
  183. Zhou X, Zhu H, Liu L et al (2010) A review: recent advances and future prospects of taxol-producing endophytic fungi. Appl Microbiol Biotechnol 86:1707–1717. CrossRefPubMedGoogle Scholar
  184. Zuccaro A, Lahrmann U, Güldener U et al (2011) Endophytic life strategies decoded by genome and transcriptome analyses of the mutualistic root symbiont Piriformospora indica. PLoS Pathog 7:e1002290. CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Khwajah Mohinudeen
    • 1
  • Karthik Devan
    • 1
  • Smita Srivastava
    • 1
    Email author
  1. 1.Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences BuildingIndian Institute of Technology MadrasChennaiIndia

Personalised recommendations