Endophytes as a Source of High-Value Phytochemicals: Present Scenario and Future Outlook

  • Vijay Lakshmi Jamwal
  • Sumit G. GandhiEmail author
Reference work entry
Part of the Reference Series in Phytochemistry book series (RSP)


Endophytes, a group of microorganisms that reside within plants, are promising eco-friendly source of high-valued bioactive phytochemicals that are produced by their host. Some of the well-known examples of phytochemicals produced by endophytes are Taxol, camptothecin, azadirachtin, podophyllotoxin, vinca alkaloids, cinchona alkaloids rohitukine, and many others. The molecular machinery for production of phytochemicals in endophytes is likely acquired from the host plant. After growing in axenic conditions for a few generations, the endophyte generally undergoes attenuation, and the production of phytochemical may reduce to a great extent or stop completely. Genome sequencing of several endophytes revealed that complete biosynthetic pathways for production of phytochemicals may not be present or if present the genes may not be homologous to the plant genes. Other possible reasons for attenuation as well as experimental methods through which the issue of attenuation may be addressed have also been discussed in the chapter.


Attenuation Bioactive Biosynthetic pathway Mutualism Plant-microbe interactions Secondary metabolism Symbiosis 


  1. 1.
    Verdine GL (1996) The combinatorial chemistry of nature. Nature 384(6604 Suppl):11–13Google Scholar
  2. 2.
    Gandhi SG, Mahajan V, Bedi YS (2015) Changing trends in biotechnology of secondary metabolism in medicinal and aromatic plants. Planta 241(2):303–317PubMedCrossRefGoogle Scholar
  3. 3.
    Uniyal SK (2013) Bark removal and population structure of Taxus wallichiana Zucc. in a temperate mixed conifer forest of western Himalaya. Environ Monit Assess 185(4):2921–2928PubMedCrossRefGoogle Scholar
  4. 4.
    Mahajan V, Sharma N, Kumar S, Bhardwaj V, Ali A, Khajuria RK, Bedi YS, Vishwakarma RA, Gandhi SG (2015) Production of rohitukine in leaves and seeds of Dysoxylum binectariferum: an alternate renewable resource. Pharm Biol 53(3):446–450PubMedCrossRefGoogle Scholar
  5. 5.
    DeBary A (1866) Morphologie und Physiologie der Pilze, Flechten, und Myxomyceten. Vol. 2 Hofmeister’s Handbook of physiological botany. Engelmann, LeipzigGoogle Scholar
  6. 6.
    George C (1988) Fungal endophytes in stems and leaves: from latent pathogen to mutualistic symbiont. Ecology 69(1):2–9CrossRefGoogle Scholar
  7. 7.
    Petrini O (1991) Fungal endophytes of tree leaves. Springer, New YorkCrossRefGoogle Scholar
  8. 8.
    Stone J, Bacon C, White JJ (2000) An overview of endophytic microbes: endophytism defined. In: microbial endophytes, Marcel-Dekker, New York. pp 3–30Google Scholar
  9. 9.
    Guerin P (1898) Sur la présence d’un champignon dans l’ivraie. J Bot 12:230–238Google Scholar
  10. 10.
    Bacon CW, Porter JK, Robbins JD, Luttrell ES (1977) Epichloe typhina from toxic tall fescue grasses. Appl Environ Microbiol 34(5):576–581PubMedPubMedCentralGoogle Scholar
  11. 11.
    Rodriguez RJ, Redman RS, Henson JM (2004) The role of fungal symbioses in the adaptation of plants to high stress environments. Mitig Adapt Strateg Glob Chang 9(3):261–272CrossRefGoogle Scholar
  12. 12.
    Rodriguez RJ, Henson J, Van Volkenburgh E, Hoy M, Wright L, Beckwith F, Kim Y-O, Redman RS (2008) Stress tolerance in plants via habitat-adapted symbiosis. ISME J 2(4):404CrossRefGoogle Scholar
  13. 13.
    Strobel G, Daisy B, Castillo U, Harper J (2004) Natural products from endophytic microorganisms. J Nat Prod 67(2):257–268CrossRefGoogle Scholar
  14. 14.
    Staniek A, Woerdenbag HJ, Kayser O (2008) Endophytes: exploiting biodiversity for the improvement of natural product-based drug discovery. J Plant Interact 3(2):75–93CrossRefGoogle Scholar
  15. 15.
    Aly AH, Debbab A, Kjer J, Proksch P (2010) Fungal endophytes from higher plants: a prolific source of phytochemicals and other bioactive natural products. Fungal Divers 41(1):1–16CrossRefGoogle Scholar
  16. 16.
    Kharwar RN, Mishra A, Gond SK, Stierle A, Stierle D (2011) Anticancer compounds derived from fungal endophytes: their importance and future challenges. Nat Prod Rep 28(7): 1208–1228CrossRefGoogle Scholar
  17. 17.
    Kusari S, Spiteller M (2012) Metabolomics of endophytic fungi producing associated plant secondary metabolites: progress, challenges and opportunities. In: Metabolomics. InTech, RijekaGoogle Scholar
  18. 18.
    Stierle A, Strobel G, Stierle D (1993) Taxol and taxane production by Taxomyces andreanae, an endophytic fungus of Pacific yew. Science 260(5105):214–216CrossRefGoogle Scholar
  19. 19.
    Eyberger AL, Dondapati R, Porter JR (2006) Endophyte fungal isolates from Podophyllum peltatum produce podophyllotoxin. J Nat Prod 69(8):1121–1124PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Puri SC, Nazir A, Chawla R, Arora R, Riyaz-ul-Hasan S, Amna T, Ahmed B, Verma V, Singh S, Sagar R (2006) The endophytic fungus Trametes hirsuta as a novel alternative source of podophyllotoxin and related aryl tetralin lignans. J Biotechnol 122(4):494–510CrossRefGoogle Scholar
  21. 21.
    Kusari S, Lamshöft M, Spiteller M (2009) 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(3):1019–1030PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Puri SC, Verma V, Amna T, Qazi GN, Spiteller M (2005) An endophytic fungus from Nothapodytes foetida that produces Camptothecin. J Nat Prod 68(12):1717–1719CrossRefGoogle Scholar
  23. 23.
    Kusari S, Zühlke S, Spiteller M (2009) An endophytic fungus from Camptotheca acuminata that produces camptothecin and analogues. J Nat Prod 72(1):2–7CrossRefGoogle Scholar
  24. 24.
    Shweta S, Zuehlke S, Ramesha B, Priti V, Kumar PM, Ravikanth G, Spiteller M, Vasudeva R, Shaanker RU (2010) Endophytic fungal strains of Fusarium solani, from Apodytes dimidiata E. Mey. ex Arn (Icacinaceae) produce camptothecin, 10-hydroxycamptothecin and 9-methoxycamptothecin. Phytochemistry 71(1):117–122CrossRefGoogle Scholar
  25. 25.
    Kusari S, Lamshöft M, Zühlke S, Spiteller M (2008) An endophytic fungus from Hypericum perforatum that produces hypericin. J Nat Prod 71(2):159–162CrossRefGoogle Scholar
  26. 26.
    Kusari S, Zühlke S, Kosuth J, Cellarova E, Spiteller M (2009) Light-independent metabolomics of endophytic Thielavia subthermophila provides insight into microbial hypericin biosynthesis. J Nat Prod 72(10):1825–1835PubMedCrossRefGoogle Scholar
  27. 27.
    Kusari S, Verma VC, Lamshoeft M, Spiteller M (2012) An endophytic fungus from Azadirachta indica A. Juss. that produces azadirachtin. World J Microbiol Biotechnol 28(3):1287–1294CrossRefGoogle Scholar
  28. 28.
    Horwitz SB, Cohen D, Rao S, Ringel I, Shen H-J, Yang C (1993) Taxol: mechanisms of action and resistance. J Natl Cancer Inst Monogr 15:55–61Google Scholar
  29. 29.
    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 Intern Med 111(4):273–279PubMedCrossRefGoogle Scholar
  30. 30.
    Einzig AI, Wiernik PH, Schwartz EL (1992) Taxol: a new agent active in melanoma and ovarian cancer. In: New drugs, concepts and results in cancer chemotherapy. Springer, BostonGoogle Scholar
  31. 31.
    Markman M (1991) Taxol: an important new drug in the management of epithelial ovarian cancer. Yale J Biol Med 64(6):583PubMedPubMedCentralGoogle Scholar
  32. 32.
    Wani M (1972) Plant antitumor agents. VI. The isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia. J Am Chem Soc 19:2325–2326Google Scholar
  33. 33.
    Majumder A, Jha S (2009) Biotechnological approaches for the production of potential anticancer leads podophyllotoxin and paclitaxel: an overview. J Biol Sci 1(1):46–69Google Scholar
  34. 34.
    Kwak S-S, Choi M-S, Park Y-G, Yoo J-S, Liu J-R (1995) Taxol content in the seeds of Taxus spp. Phytochemistry 40(1):29–32CrossRefGoogle Scholar
  35. 35.
    Bedi Y, Ogra R, kiran k, Kaul B, Kapil R (1996) Yew (Taxus spp.). A new look on utilization, cultivation and conservation. In: Supplement to cultivation and utilization of medicinal plants. Regional Research Laboratory Jammu-Tawi (India). pp 443–456Google Scholar
  36. 36.
    Strobel GA, Hess W, Li J-Y, 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(6):1073–1082CrossRefGoogle Scholar
  37. 37.
    Gangadevi V, Muthumary J (2009) Taxol production by Pestalotiopsis terminaliae, an endophytic fungus of Terminalia arjuna (arjun tree). Biotechnol Appl Biochem 52(1):9–15PubMedCrossRefGoogle Scholar
  38. 38.
    Senthil Kumaran R, Muthumary J, Hur B (2008) Production of taxol from Phyllosticta spinarum, an endophytic fungus of Cupressus sp. Eng Life Sci 8(4):438–446CrossRefGoogle Scholar
  39. 39.
    Kim S (1999) Screening of taxol-producing endophytic fungi from Ginkgo biloba and Taxus cuspidate in Korea. Agric Chem Biotechnol 42:97–99Google Scholar
  40. 40.
    Kumaran RS, Muthumary J, Kim E-K, Hur B-K (2009) Production of taxol from Phyllosticta dioscoreae, a leaf spot fungus isolated from Hibiscus rosa-sinensis. Biotechnol Bioprocess Eng 14(1):76CrossRefGoogle Scholar
  41. 41.
    Sun D, Ran X, Wang J (2008) Isolation and identification of a taxol-producing endophytic fungus from Podocarpus. Acta Microbiol Sin 48(5):589–595Google Scholar
  42. 42.
    Gangadevi V, Murugan M, Muthumary J (2008) Taxol determination from Pestalotiopsis pauciseta, a fungal endophyte of a medicinal plant. Chin J Biotechnol 24(8):1433–1438CrossRefGoogle Scholar
  43. 43.
    Venkatachalam R, Subban K, Paul MJ (2008) Taxol from Botryodiplodia theobromae (BT 115) – AN endophytic fungus of Taxus baccata. J Biotechnol 136:S189–S190CrossRefGoogle Scholar
  44. 44.
    Chakravarthi B, Das P, Surendranath K, Karande AA, Jayabaskaran C (2008) Production of paclitaxel by Fusarium solani isolated from Taxus celebica. J Biosci 33(2):259PubMedCrossRefGoogle Scholar
  45. 45.
    Deng BW, Liu KH, Chen WQ, Ding XW, Xie XC (2009) Fusariumásolani, Tax-3, a new endophytic taxol-producing fungus from Taxus chinensis. World J Microbiol Biotechnol 25(1):139CrossRefGoogle Scholar
  46. 46.
    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(9):1171PubMedCrossRefGoogle Scholar
  47. 47.
    Zhou X, Wang Z, Jiang K, Wei Y, Lin J, Sun X, Tang K (2007) Screening of taxol-producing endophytic fungi from Taxus chinensis var. mairei. Appl Biochem Microbiol 43(4):439–443CrossRefGoogle Scholar
  48. 48.
    Guo BH, Wang Y, Zhou X, Hu K, Tan F, Miao Z, Tang K (2006) An endophytic Taxol-producing fungus BT2 isolated from Taxus Chinensis var. mairei. Afr J Biotechnol 5(10):875–877Google Scholar
  49. 49.
    Wu L-S, Hu C-L, Han T, Zheng C-J, Ma X-Q, Rahman K, Qin L-P (2013) Cytotoxic metabolites from Perenniporia tephropora, an endophytic fungus from Taxus chinensis var. mairei. Appl Microbiol Biotechnol 97(1):305–315CrossRefGoogle Scholar
  50. 50.
    Zhang P, Zhou P-P, Yu L-J (2009) An endophytic taxol-producing fungus from Taxus media, Cladosporium cladosporioides MD2. Curr Microbiol 59(3):227CrossRefGoogle Scholar
  51. 51.
    Strobel GA, Hess WM, Ford E, Sidhu R, Yang X (1996) Taxol from fungal endophytes and the issue of biodiversity. J Ind Microbiol 17(5–6):417–423Google Scholar
  52. 52.
    Qiu D, Huang M, Fang X, Zhu C, Zhu Z (1994) Isolation of an endophytic fungus associated with Taxus yunnanensis Cheng et LK Fu. Acta Mycol Sin 13(4):314–316Google Scholar
  53. 53.
    Li J-y, Strobel G, Sidhu R, Hess W, Ford EJ (1996) Endophytic taxol-producing fungi from bald cypress, Taxodium distichum. Microbiology 142(8):2223–2226PubMedCrossRefGoogle Scholar
  54. 54.
    Shrestha K, Strobel GA, Shrivastava SP, Gewali MB (2001) Evidence for paclitaxel from three new endophytic fungi of Himalayan yew of Nepal. Planta Med 67(04):374–376PubMedCrossRefGoogle Scholar
  55. 55.
    Li JY, Sidhu RS, Ford E, Long D, Hess W, Strobel G (1998) The induction of taxol production in the endophytic fungus – Periconia sp. from Torreya grandifolia. J Ind Microbiol Biotechnol 20(5):259–264CrossRefGoogle Scholar
  56. 56.
    Guo B, Li H, Zhang L (1998) Isolation of an fungus producing vinblastine. J Yunnan Univ (Nat Sci) 20(3):214–215Google Scholar
  57. 57.
    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 Herb Drug 31(11):805–807Google Scholar
  58. 58.
    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(7):1115–1121CrossRefGoogle Scholar
  59. 59.
    Liang Z, Zhang J, Zhang X, Li J, Zhang X, Zhao C (2015) Endophytic fungus from Sinopodophyllum emodi (Wall.) Ying that produces podophyllotoxin. J Chromatogr Sci 54(2):175–178PubMedGoogle Scholar
  60. 60.
    Zeng S, Ke Y, Fang B, Zhang L-q (2005) Diversity and correlation of endophytic fungi and rhizosphere fungi isolated from Diphylleia sinensis. J Zhuzhou Inst Technol 19(001):25–27Google Scholar
  61. 61.
    Li C (2007) Fermentation conditions of Sinopodophyllum hexandrum endophytic fungus on production of podophyllotoxin. Food Ferment Ind 33(9):28Google Scholar
  62. 62.
    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(4): 254–259Google Scholar
  63. 63.
    Ju Z, Wang J, Pan S (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 4:017Google Scholar
  64. 64.
    Zhou X, Zheng W, Zhu H (2009) Identification of a taxol-producing endophytic fungus EFY-36. Afr J Biotechnol 8(11):2623–2625Google Scholar
  65. 65.
    Kumara PM, Zuehlke S, Priti V, Ramesha BT, Shweta S, Ravikanth G, Vasudeva R, Santhoshkumar TR, Spiteller M, Shaanker RU (2012) Fusarium proliferatum, an endophytic fungus from Dysoxylum binectariferum Hook. f, produces rohitukine, a chromane alkaloid possessing anti-cancer activity. Antonie Van Leeuwenhoek 101(2):323–329CrossRefGoogle Scholar
  66. 66.
    Maehara S, Simanjuntak P, Kitamura C, Ohashi K, Shibuya H (2011) Cinchona alkaloids are also produced by an endophytic filamentous fungus living in Cinchona plant. Chem Pharm Bull 59(8):1073–1074PubMedCrossRefGoogle Scholar
  67. 67.
    Duan L, Liwei G, Hong Y (2009) Isolation and identification of producing endophytic fungi of berberine from the plant Phellodendron amurense. J Anhui Agric Sci 22(007).
  68. 68.
    Yin H, Chen J-L (2008) Sipeimine-producing endophytic fungus isolated from. Z Naturforsch C 63(11–12):789–793PubMedCrossRefGoogle Scholar
  69. 69.
    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(5):447–454PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Zhao J, Fu Y, Luo M, Zu Y, Wang W, Zhao C, Gu C (2012) Endophytic fungi from pigeon pea [Cajanus cajan (L.) Millsp.] produce antioxidant cajaninstilbene acid. J Agric Food Chem 60(17):4314–4319PubMedCrossRefGoogle Scholar
  71. 71.
    Chen M, Yang L, Li Q, Shen Y, Shao A, Lin S, Huang L (2011) Volatile metabolites analysis and molecular identification of endophytic fungi bn12 from Cinnamomum camphora chvar. borneol. China J Chin Materia Medica 36(23):3217–3221Google Scholar
  72. 72.
    Cui Y, Yi D, Bai X, Sun B, Zhao Y, Zhang Y (2012) Ginkgolide B produced endophytic fungus (Fusarium oxysporum) isolated from Ginkgo biloba. Fitoterapia 83(5):913–920CrossRefGoogle Scholar
  73. 73.
    Pan F, Su X, Hu B, Yang N, Chen Q, Wu W (2015) Fusarium redolens 6WBY3, an endophytic fungus isolated from Fritillaria unibracteata var. wabuensis, produces peimisine and imperialine-3β-d-glucoside. Fitoterapia 103:213–221CrossRefGoogle Scholar
  74. 74.
    Chithra S, Jasim B, Sachidanandan P, Jyothis M, Radhakrishnan E (2014) Piperine production by endophytic fungus Colletotrichum gloeosporioides isolated from Piper nigrum. Phytomedicine 21(4):534–540PubMedCrossRefGoogle Scholar
  75. 75.
    Haque MA, Hossain MS, Rahman M, Rahman MR, Hossain MS, Mosihuzzaman M, Nahar N, Khan S (2005) Isolation of bioactive secondary metabolites from the endophytic fungus of Ocimum basilicum. J Pharm Sci 4(2):127–13012Google Scholar
  76. 76.
    Turbyville TJ, Wijeratne EK, Liu MX, Burns AM, Seliga CJ, Luevano LA, David CL, Faeth SH, Whitesell L, Gunatilaka AL (2006) Search for Hsp90 inhibitors with potential anticancer activity: isolation and SAR studies of radicicol and monocillin I from two plant-associated fungi of the Sonoran desert. J Nat Prod 69(2):178–184PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Redko F, Clavin M, Weber D, Anke T, Martino V (2006) Search for active metabolites of Erythrina crista-galli and its endophyte Phomopsis sp. Mol Med Chem 10:24–26Google Scholar
  78. 78.
    Strobel GA, Kluck K, Hess WM, Sears J, Ezra D, Vargas PN (2007) Muscodor albus E-6, an endophyte of Guazuma ulmifolia making volatile antibiotics: isolation, characterization and experimental establishment in the host plant. Microbiology 153(8):2613–2620PubMedCrossRefGoogle Scholar
  79. 79.
    Campos FF, Rosa LH, Cota BB, Caligiorne RB, Rabello ALT, Alves TMA, Rosa CA, Zani CL (2008) Leishmanicidal metabolites from Cochliobolus sp., an endophytic fungus isolated from Piptadenia adiantoides (Fabaceae). PLoS Negl Trop Dis 2(12):e348PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Liu X, Dong M, Chen X, Jiang M, Lv X, Zhou J (2008) Antimicrobial activity of an endophytic Xylaria sp. YX-28 and identification of its antimicrobial compound 7-amino-4-methylcoumarin. Appl Microbiol Biotechnol 78(2):241–247PubMedCrossRefGoogle Scholar
  81. 81.
    Nithya K, Muthumary J (2010) Secondary metabolite from Phomopsis sp. isolated from Plumeria acutifolia Poiret. Recent Res Sci Technol 2(4):99Google Scholar
  82. 82.
    Yu H, Zhang L, Li L, Zheng C, Guo L, Li W, Sun P, Qin L (2010) Recent developments and future prospects of antimicrobial metabolites produced by endophytes. Microbiol Res 165(6):437–449PubMedCrossRefGoogle Scholar
  83. 83.
    Saxena S, Meshram V, Kapoor N (2015) Muscodor tigerii sp. nov.-volatile antibiotic producing endophytic fungus from the Northeastern Himalayas. Ann Microbiol 65(1):47–57CrossRefGoogle Scholar
  84. 84.
    Suwannarach N, Kumla J, Bussaban B, Nuangmek W, Matsui K, Lumyong S (2013) Biofumigation with the endophytic fungus Nodulisporium spp. CMU-UPE34 to control postharvest decay of citrus fruit. Crop Prot 45:63–70CrossRefGoogle Scholar
  85. 85.
    Gao J, Xu A, Tang X (2011) Isolation, identification and volatile compound analysis of an aroma-producing endophytic yeast from romaine lettuce. Food Sci 23:33Google Scholar
  86. 86.
    Trapp MA, Kai M, Mithöfer A, Rodrigues-Filho E (2015) Antibiotic oxylipins from Alternanthera brasiliana and its endophytic bacteria. Phytochemistry 110:72–82PubMedCrossRefGoogle Scholar
  87. 87.
    Harmon AD, Weiss U, Silverton J (1979) The structure of rohitukine, the main alkaloid of Amoora rohituka (Syn. Aphanamixis polystachya)(meliaceae). Tetrahedron Lett 20(8): 721–724CrossRefGoogle Scholar
  88. 88.
    Li Q-Y, Zu Y-G, Shi R-Z, Yao L-P (2006) Review camptothecin: current perspectives. Curr Med Chem 13(17):2021–2039PubMedCrossRefGoogle Scholar
  89. 89.
    Canel C, Moraes RM, Dayan FE, Ferreira D (2000) Podophyllotoxin. Phytochemistry 54(2): 115–120PubMedCrossRefGoogle Scholar
  90. 90.
    Song CE (2009) An overview of Cinchona alkaloids in chemistry. In: Cinchona alkaloids in synthesis and catalysis: ligands, immobilization and organocatalysis, Wiley-VCH, Weinheim. pp 1–10Google Scholar
  91. 91.
    Groppe K, Steinger T, Sanders I, Schmid B, Wiemken A, Boller T (1999) Interaction between the endophytic fungus Epichloë bromicola and the grass Bromus erectus: effects of endophyte infection, fungal concentration and environment on grass growth and flowering. Mol Ecol 8(11):1827–1835PubMedCrossRefGoogle Scholar
  92. 92.
    Strobel G, Daisy B (2003) Bioprospecting for microbial endophytes and their natural products. Microbiol Mol Biol Rev 67(4):491–502PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Zhang HW, Song YC, Tan RX (2006) Biology and chemistry of endophytes. Nat Prod Rep 23(5):753–771CrossRefGoogle Scholar
  94. 94.
    Mitter B, Petric A, Shin MW, Chain PS, Hauberg-Lotte L, Reinhold-Hurek B, Nowak J, Sessitsch A (2013) Comparative genome analysis of Burkholderia phytofirmans PsJN reveals a wide spectrum of endophytic lifestyles based on interaction strategies with host plants. Front Plant Sci 4:120PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Schulthess FM, Faeth SH (1998) Distribution, abundances, and associations of the endophytic fungal community of Arizona fescue (Festuca arizonica). Mycologia 90:569–578CrossRefGoogle Scholar
  96. 96.
    Germaine K, Keogh E, Garcia-Cabellos G, Borremans B, Van Der Lelie D, Barac T, Oeyen L, Vangronsveld J, Moore FP, Moore ER (2004) Colonisation of poplar trees by GFP expressing bacterial endophytes. FEMS Microbiol Ecol 48(1):109–118PubMedCrossRefGoogle Scholar
  97. 97.
    Gunatilaka AL (2006) Natural products from plant-associated microorganisms: distribution, structural diversity, bioactivity, and implications of their occurrence. J Nat Prod 69(3):509–526PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Frisvad JC, Andersen B, Thrane U (2008) The use of secondary metabolite profiling in chemotaxonomy of filamentous fungi. Mycol Res 112(2):231–240PubMedCrossRefGoogle Scholar
  99. 99.
    Kirby J, Keasling JD (2009) Biosynthesis of plant isoprenoids: perspectives for microbial engineering. Annu Rev Plant Biol 60:335–355PubMedCrossRefGoogle Scholar
  100. 100.
    Schulz B, Römmert A-K, Dammann U, Aust H-J, Strack D (1999) The endophyte-host interaction: a balanced antagonism? Mycol Res 103(10):1275–1283CrossRefGoogle Scholar
  101. 101.
    Schulz B, Boyle C (2005) The endophytic continuum. Mycol Res 109(6):661–686CrossRefGoogle Scholar
  102. 102.
    Kusari S, Spiteller M (2011) Are we ready for industrial production of bioactive plant secondary metabolites utilizing endophytes? Nat Prod Rep 28(7):1203–1207PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Howitz KT, Sinclair DA (2008) Xenohormesis: sensing the chemical cues of other species. Cell 133(3):387–391PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Owen NL, Hundley N (2004) Endophytes–the chemical synthesizers inside plants. Sci Prog 87(2):79–99CrossRefGoogle Scholar
  105. 105.
    Frey M, Chomet P, Glawischnig E, Stettner C, Grün S, Winklmair A, Eisenreich W, Bacher A, Meeley RB, Briggs SP (1997) Analysis of a chemical plant defense mechanism in grasses. Science 277(5326):696–699PubMedCrossRefGoogle Scholar
  106. 106.
    Kirby R, Hopwood D (1977) Genetic determination of methylenomycin synthesis by the SCP1 plasmid of Streptomyces coelicolor A3 (2). Microbiology 98(1):239–252CrossRefGoogle Scholar
  107. 107.
    Mochizuki S, Hiratsu K, Suwa M, Ishii T, Sugino F, Yamada K, Kinashi H (2003) The large linear plasmid pSLA2-L of Streptomyces rochei has an unusually condensed gene organization for secondary metabolism. Mol Microbiol 48(6):1501–1510PubMedCrossRefGoogle Scholar
  108. 108.
    Priti V, Ramesha B, Singh S, Ravikanth G, Ganeshaiah K, Suryanarayanan T, Uma Shaanker R (2009) How promising are endophytic fungi as alternative sources of plant secondary metabolites? Curr Sci 97(4):477–478Google Scholar
  109. 109.
    Shwab EK, Keller NP (2008) Regulation of secondary metabolite production in filamentous ascomycetes. Mycol Res 112(2):225–230CrossRefGoogle Scholar
  110. 110.
    Kusari S, Zuhlke S, Spiteller M (2011) Effect of artificial reconstitution of the interaction between the plant Camptotheca acuminata and the fungal endophyte Fusarium solani on camptothecin biosynthesis. J Nat Prod 74(4):764–775CrossRefGoogle Scholar
  111. 111.
    Keller L, Surette MG (2006) Communication in bacteria: an ecological and evolutionary perspective. Nat Rev Microbiol 4(4):249PubMedCrossRefGoogle Scholar
  112. 112.
    Hughes DT, Sperandio V (2008) Inter-kingdom signalling: communication between bacteria and their hosts. Nat Rev Microbiol 6(2):111PubMedPubMedCentralCrossRefGoogle Scholar
  113. 113.
    Scherlach K, Hertweck C (2009) Triggering cryptic natural product biosynthesis in microorganisms. Org Biomol Chem 7(9):1753–1760CrossRefGoogle Scholar
  114. 114.
    Kumara PM, Soujanya K, Ravikanth G, Vasudeva R, Ganeshaiah K, Shaanker RU (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(4):541–546PubMedCrossRefGoogle Scholar
  115. 115.
    Partida-Martinez LP, Hertweck C (2005) Pathogenic fungus harbours endosymbiotic bacteria for toxin production. Nature 437(7060):884PubMedCrossRefGoogle Scholar
  116. 116.
    Schroeckh V, Scherlach K, Nützmann H-W, Shelest E, Schmidt-Heck W, Schuemann J, Martin K, Hertweck C, Brakhage AA (2009) Intimate bacterial–fungal interaction triggers biosynthesis of archetypal polyketides in Aspergillus nidulans. Proc Natl Acad Sci 106(34): 14558–14563CrossRefGoogle Scholar
  117. 117.
    Vasanthakumari M, Jadhav S, Sachin N, Vinod G, Shweta S, Manjunatha B, Kumara PM, Ravikanth G, Nataraja KN, Shaanker RU (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(10):1629–1639CrossRefGoogle Scholar
  118. 118.
    Venugopalan A, Srivastava S (2015) Enhanced camptothecin production by ethanol addition in the suspension culture of the endophyte, Fusarium solani. Bioresour Technol 188:251–257PubMedCrossRefGoogle Scholar
  119. 119.
    Winter JM, Behnken S, Hertweck C (2011) Genomics-inspired discovery of natural products. Curr Opin Chem Biol 15(1):22–31PubMedCrossRefGoogle Scholar
  120. 120.
    Field B, Osbourn AE (2008) Metabolic diversification – independent assembly of operon-like gene clusters in different plants. Science 320(5875):543–547PubMedCrossRefGoogle Scholar
  121. 121.
    Osbourn A, Papadopoulou KK, Qi X, Field B, Wegel E (2012) Finding and analyzing plant metabolic gene clusters. In: Methods in enzymology. Elsevier, Academic Press, New York. pp 517:113–38Google Scholar
  122. 122.
    Castillo DA, Kolesnikova MD, Matsuda SP (2013) An effective strategy for exploring unknown metabolic pathways by genome mining. J Am Chem Soc 135(15):5885–5894PubMedCrossRefGoogle Scholar
  123. 123.
    Cyr A, Wilderman PR, Determan M, Peters RJ (2007) A modular approach for facile biosynthesis of labdane-related diterpenes. J Am Chem Soc 129(21):6684–6685PubMedPubMedCentralCrossRefGoogle Scholar
  124. 124.
    Nakagawa A, Minami H, Kim J-S, Koyanagi T, Katayama T, Sato F, Kumagai H (2011) A bacterial platform for fermentative production of plant alkaloids. Nat Commun 2:326PubMedPubMedCentralCrossRefGoogle Scholar
  125. 125.
    Siddiqui MS, Thodey K, Trenchard I, Smolke CD (2012) Advancing secondary metabolite biosynthesis in yeast with synthetic biology tools. FEMS Yeast Res 12(2):144–170PubMedCrossRefGoogle Scholar
  126. 126.
    Paddon CJ, Westfall PJ, Pitera DJ, Benjamin K, Fisher K, McPhee D, Leavell M, Tai A, Main A, Eng D (2013) High-level semi-synthetic production of the potent antimalarial artemisinin. Nature 496(7446):528PubMedCrossRefGoogle Scholar
  127. 127.
    Westfall PJ, Pitera DJ, Lenihan JR, Eng D, Woolard FX, Regentin R, Horning T, Tsuruta H, Melis DJ, Owens A (2012) Production of amorphadiene in yeast, and its conversion to dihydroartemisinic acid, precursor to the antimalarial agent artemisinin. Proc Natl Acad Sci 109(3):E111–E118PubMedCrossRefGoogle Scholar
  128. 128.
    Wei Y, Liu L, Zhou X, Lin J, Sun X, Tang K (2012) Engineering taxol biosynthetic pathway for improving taxol yield in taxol-producing endophytic fungus EFY-21 (Ozonium sp.). Afr J Biotechnol 11(37):9094–9101Google Scholar
  129. 129.
    Kai Z, Xuan W, Yushi S, Ying W, Wenxiang P, Dongpo Z (2008) Screening of high taxol producing fungi by NTG combining with UV mutagenesis. J Nat Sci Heilongjiang Univ 1:016Google Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Plant Biotechnology DivisionCSIR-Indian Institute of Integrative MedicineJammuIndia

Personalised recommendations