Endophytes of Nothapodytes nimmoniana (J. Graham) Mabb.

  • Hosakatte Niranjana MurthyEmail author
  • Dayanand Dalawai
  • So-Young Park
  • Kee-Yoeup Paek
Reference work entry
Part of the Reference Series in Phytochemistry book series (RSP)


Endophytes are excellent source of bioactive natural products. Fungal and bacterial endophytes have been isolated from medicinal plant Nothapodytes nimmoniana, and majority of them have the capability of accumulating camptothecin (CPT) similar to host plant. Entrophospora infrequens, Neurospora crassa, Fusarium oxysporum, Colletotrichum fructicola, and Corynespora cassiicola are some of the fungal isolates which have been cultured by following submerged fermentation and solid-state fermentation methods for the production of CPT. Here we presented the detailed account of various endophytes isolated from Nothapodytes nimmoniana and recent research developments made in this area.


Axenic cultures Bioactive compounds Camptothecin Endophytes Fermentation Secondary metabolites 





Adenocarcinomic human alveolar basal epithelial cells (lung cancer cell line)


Beef extract broth


Biological oxygen demand


Central composite design


Czapek dox broth


Chemical oxygen demand




US Food and Drug Administration


Human epithelial type 2 (liver cancer cell line)


High performance liquid chromatography


Liquid chromatography/mass spectroscopy


Malt extract broth


Mass spectroscopy/mass spectroscopy


Human epithelial carcinoma cell line of the ovary (ovarian cancer cell line)


Potato dextrose broth


Response surface methodology


Sabouraud broth


Solid-state fermentation


Total dissolved solids


Total soluble solids


Yeast extract broth



This study was supported by DST-PURSE Phase II program and UGC-BSR Mid-Career Award grant [No. F.19-223/2018(BSR)].


  1. 1.
    Nothapodytes nimmoniana (J. Graham) Mabb. In GBIF Secretariat (2017) GBIF Backbone Taxonomy. Checklist Dataset accessed via
  2. 2.
    Hombegowda HC, Vasudeva R, Mathachen GP, Uma Shaanker R, Ganeshaiah KN (2002) Breeding types in Nothapodytes nimmoniana Graham: an important medicinal tree. Curr Sci 83:1077–1078Google Scholar
  3. 3.
    Govindachari T, Vishwanathan N (1972) Alkaloids of Mappia foetida. Phytochemistry 11:3529–3531CrossRefGoogle Scholar
  4. 4.
    Wu TS, Leu YL, Hsu HC, Ou LF, Chen CC, Chen CF, Ou JC, Wu YC (1995) Constituents and cytotoxic principles of Nothapodytes foetida. Phytochemistry 39:383–385CrossRefGoogle Scholar
  5. 5.
    Valdu B, Woynarowski JM, Manikumar G, Wani MC, Wall ME, Von Hoff DD, Wadkins RM (2000) 7- and 10-substituted camptothecins: dependence of topoisomerase-I DNA cleavable complex formation and stability on the 7- and 10-substitutes. Mol Pharm 57:243–251Google Scholar
  6. 6.
    Wall ME, Whal MC, Cook CE, Palmer KH, McPhail AT, Sim GA (1966) Plant antitumor agents I. The isolation and structure of camptothecin, a novel alkaloidal leukemia and tumor inhibitor from Camptotheca accuminata. J Am Chem Soc 88:3888–3890CrossRefGoogle Scholar
  7. 7.
    Lorence A, Nessler CL (2004) Camptothecin, over four decades of surprising findings. Phytochemistry 65:2735–2749CrossRefGoogle Scholar
  8. 8.
    Kai G, Wu C, Gen L, Zhang L, Cui L, Ni X (2015) Biosynthesis and biotechnological production of anti-cancer drug camptothecin. Phytochem Rev 14:525–539CrossRefGoogle Scholar
  9. 9.
    Li S, Yi Y, Wang Y, Zhang Z, Beasley RS (2002) Camptothecin accumulation and variations in Camptotheca. Plant Med 68:1010–1016CrossRefGoogle Scholar
  10. 10.
    Gunasekera SP, Badwi MM, Cordell GA, Farnsworth NR, Chitins M (1979) Plant anticancer agents X. Isolation of camptothecin and 9-methoxycamptothecin from Ervatamia heyneana. J Nat Prod 42:475–477CrossRefGoogle Scholar
  11. 11.
    Arisawa M, Gunasekera SP, Cordell GA, Farnsworth NR (1981) Plant anticancer agents XXI. Constituents from Merrilliodendron megacarpum. Plant Med 43:404–407CrossRefGoogle Scholar
  12. 12.
    Dai JR, Cardellina JH, Boyd MR (1999) 20-Ob-glucopyranosyl camptothecin from Mostuea brunonis: a potential camptothecin pro-drug with improved solubility. J Nat Prod 62:1427–1429CrossRefGoogle Scholar
  13. 13.
    Aiyama R, Nagai H, Nokata K, Shinohara C, Sawada S (1988) A camptothecin derivative from Nothapodytes foetida. Phytochemistry 27:3663–3664CrossRefGoogle Scholar
  14. 14.
    Roja G, Heble MR (1994) The quinoline alkaloids camptothecin and 9-methoxycamptothecin from tissue cultures and mature trees of Nothapodytes foetida. Phytochemistry 36:65–66CrossRefGoogle Scholar
  15. 15.
    Padmanabha BV, Chadrashekar M, Ramesha BT, Hombegowda HC, Gunaga RP, Suhas S, Vasudeva R, Ganeshaiah KN, Uma Shaanker R (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 90:95–100Google Scholar
  16. 16.
    Yamazaki Y, Urano A, Sudo H, Kitajima M, Takayama H, Yamazaki M, Aimi N, Saito K (2003) Metabolite profiling of alkaloids and strictosidine synthase activity in camptothecin producing plants. Phytochemistry 62:461–470CrossRefGoogle Scholar
  17. 17.
    Tafur S, Nelson JD, DeLong DC, Svoboda GH (1976) Antiviral components of Ophiorrhiza mungos, isolation of camptothecin and 10-methoxycamptothecin. Lolydia 39:261–262Google Scholar
  18. 18.
    Saito K, Sudo M, Yamazaki M, Koeski-Nakamura M, Kitjima M, Takayama H, Aimi N (2001) Feasible production of camptothecin by hairy root culture of Ophiorrhiza pumila. Plant Cell Rep 20:267–271CrossRefGoogle Scholar
  19. 19.
    Fijesh VRV, Louis PVJ, Jaimsha VK, Padikkala J (2007) In vitro production of camptothecin (an anticancer drug) through albino plants of Ophiorrhiza rugosa var. documbens. Curr Sci 49:1216–1218Google Scholar
  20. 20.
    Venugopalan A, Srivastava S (2015) Endophytes as in vitro production platforms of high value plant secondary metabolites. Biotechnol Adv 33:873–887CrossRefGoogle Scholar
  21. 21.
    Kusari S, Hertweck C, Spiteller M (2012) Chemical ecology of endophytic fungi: origins of secondary metabolites. Chem Biol 19:792–798CrossRefGoogle Scholar
  22. 22.
    Strobel GA, Daisy B, Castillo U, Harper J (2004) Natural products from endophytic microorganisms. J Nat Prod 67:257–268CrossRefGoogle Scholar
  23. 23.
    Strobel G, Daisy B (2003) Bioprospecting for microbial endophytes and their natural products. Microbiol Mol Biol Rev 67:491–502CrossRefGoogle Scholar
  24. 24.
    Patil CR (2009) Studies on endorhizosphere bacteria of Nothapodytes nimmoniana and their influence on plant growth and comptothecin content. Doctoral thesis, University of Agricultural Sciences, DharwadGoogle Scholar
  25. 25.
    Puri SC, Verma V, Amna T, Qazi GN, Spiteller M (2005) An endophytic fungus from Nothapodytes foetida that produces camptothecin. J Nat Prod 68:1717–1719CrossRefGoogle Scholar
  26. 26.
    Amna T, Puri SC, Verma V, Sharma JP, Khjuria 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 52:189–196CrossRefGoogle Scholar
  27. 27.
    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 44:203–209CrossRefGoogle Scholar
  28. 28.
    Nagaraja TG (2011) Seasonal distribution of endomycophytes of medicinal plant Nothapodytes nimmoniana (J. Graham) Mabberly. J Pharm Res 4:3054–3055Google Scholar
  29. 29.
    Gurudatt PS, Priti V, Shweta S, Ramesha BT, Ravikanth G, Vasudeva R, Amna T, Deepika S, Ganeshaiah KN, Uma Shaanker R, Puri S, Qazi N (2010) Attenuation of camptothecin production and negative relation between hyphal biomass and camptothecin content in endophyte fungal strains isolated from Nothapodytes nimmoniana Grahm (Icacinaceae). Curr Sci 98:1006–1010Google Scholar
  30. 30.
    D’souza MA, Hiremath KG (2013) Composition of tissue specificity of endophytic fungi associated with Nothapodytes nimmoniana (J. Graham) Mabberly form the Western Ghats, India. Intl J Phytomed Rel Ind 5:27–33Google Scholar
  31. 31.
    Musavi SF, Dhavale A, Balakrishnan RM (2015) Optimization and kinetic modeling of cell-associated camptothecin production from an endophytic Fusarium oxysporum NFX06. Prep Biochem Biotechnol 45:158–172CrossRefGoogle Scholar
  32. 32.
    Bhalkar BN, Bedekar PA, Patil SM, Patil SA, Govindwar SP (2015) Production of camptothecine using whey by an endophytic fungus: standardization using response surface methodology. RSC Adv 5:62828–62835CrossRefGoogle Scholar
  33. 33.
    Bhalkar BN, Bedekar PA, Kshirsagar SD, Govindwar SP (2016) Solid state fermentation of soybean waste and an up-flow column bioreactor for continuous production of camptothecine by an endophytic fungus Fusarium oxysporum. RSC Adv 6:56527–56536CrossRefGoogle Scholar
  34. 34.
    Bhalkar BN, Patil SM, Govindwar SP (2016) Camptothecine production by mixed fermentation of two endophytic fungi from Nothapodytes nimmoniana. Fungal Biol 120:873–883CrossRefGoogle Scholar
  35. 35.
    Vasanthakumari MM, Jadhav SS, Sachin N, Vinod G, Shweta S, Manjunatha BL, Mohana Kumara P, Ravikanth G, Nataraja KN, Uma Shaanker R (2015) Restoration of camptothecine production in attenuated endophytic fungus on re-inoculation into host plant and treatment with DNA methyltransferase inhibitor. World J Microbiol Biotechnol 31:1629–1639CrossRefGoogle Scholar
  36. 36.
    Shweta S, Gurumurthy BR, Vasanthakumari MM, Ravikanth G, Dyanandan S, Storms R, Shivanna MB, Uma Shaanker R (2015) Endophyte fungal diversity in Nothapodytes nimmoniana along its distributional gradient in the Western Ghats, India: are comptothecine (anticancer alkaloid) producing endophytes restricted to specific clades? Curr Sci 109:127–138Google Scholar
  37. 37.
    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 23:1050–1057CrossRefGoogle Scholar
  38. 38.
    Robson T, Singh D, Nigam P (2001) Solid-state fermentation: a promising microbial technology for secondary metabolites production. Appl Microbiol Biotechnol 55:284–289CrossRefGoogle Scholar
  39. 39.
    Watanabe T, Izaki K, Takahashi H (1982) New polyenic antibiotics active against gram-positive and –negative bacteria. II. Screening of antibiotic procedures and taxonomic properties of Gluconobacter sp. W-315. J Antibiot 35:1141–1147CrossRefGoogle Scholar
  40. 40.
    Brakhage AA, Schroeckh V (2011) Fungal secondary metabolites – strategies to activate silent gene clusters. Fungal Genet Biol 48:15–22CrossRefGoogle Scholar
  41. 41.
    Sachin N, Manjunatha BL, Mohana Kumara P, Ravikanth G, Shweta S, Suryanarayana TS, Ganeshaiah KN, Uma Shaanker R (2013) Do endophytic fungi possess pathway genes for plant secondary metabolites? Curr Sci 104:178–182Google Scholar
  42. 42.
    Lopez-Meyer M, Nessler CL, McKnight TD (1994) Sites of accumulation of antitumor alkaloid camptothecin in Camptotheca accuminata. Planta Med:558–560CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Hosakatte Niranjana Murthy
    • 1
    • 2
    Email author
  • Dayanand Dalawai
    • 1
  • So-Young Park
    • 2
  • Kee-Yoeup Paek
    • 2
  1. 1.Department of BotanyKarnatak UniversityDharwadIndia
  2. 2.Research Center for the Development of Advanced Horticultural TechnologyChungbuk National UniversityCheongjuRepublic of Korea

Personalised recommendations