Host-Mimetic Metabolomics of Endophytes: Looking Back into the Future

  • Vijay Chandra Verma
  • Satya Prakash
  • Rana Gopal Singh
  • Alan Christopher Gange


Endophytic research is now gaining pace together with the technological advancement and refinements. The phenomenal potential of endophytes as prolific producer of a wide range of bioactive compounds occupies a complimentary domain of natural product research. The discovery of paclitaxel (Taxol) as bioactive natural product of endophytic origin seems to draw indisputable attention not only for their antitumor activity but as potential microbial alternative for this high in-demand drug. Plenty of opinion is given by the enthusiasts on microbial production of paclitaxel as phylogenetic process and driving paradigm of evolution; however, skeptics described it as phylogenetic anomalies. But despite being highly controversial, the horizontal gene transfer (HGT) theory still seems quite justifiable. Let’s have another example: “maytansinoid,” a potent cytotoxic agent, was isolated and characterized from microbial endophyte of the same plant; however in both cases, further investigations recorded their occurrence not only in same host but also from deferent distant hosts and even from different endophytes. So the report of taxane and related taxoids from a taxonomically distant host raises several questions. One may assume that this might be due to evolutionary invention; however, it is very unlikely to accept that all modules of gene responsible for biosynthesis of these molecules invented in microbial systems during long evolutionary symbiosis. With this chapter we are trying to get into the mechanistic aspects of host-specific chemicals synthesized by endophytic microbes together with our experience with isolation and characterization of host-specific compounds like piperine and azadirachtin. Nevertheless, the significance of this potential of endophytes cannot be ignored, as it provides not only alternative source to existing pharmaceuticals but also on the other hand save the valuable biodiversity of highly medicinal plants.


Horizontal Gene Transfer Endophytic Fungus Azadirachta Indica Antimycobacterial Activity Fungal Extract 



VCV gratefully acknowledges the financial support from University Grant Commission (wide letter No. F. 4-2/2006/13-552/2011/BSR) and Council of Scientific and Industrial Research (CSIR), New Delhi. VCV is also thankful to the Department of Science and Technology (DST), for the recognition as “Fast track young scientist” (wide letter No.: SERC/LS-515/2011).


  1. Ahmed MS, Fong HH, Soejarto DD, Dobberstein RH, Waller DP, Moreno-Azorero RJ (1981) High-performance liquid chromatographic separation and quantitation of maytansinoids in Maytenus ilicifolia. J Chromatogr 213:340–344Google Scholar
  2. Aldhous P (1992) Neem chemicals: the pieces fall in place. Science 258:893PubMedGoogle Scholar
  3. Alper H, Jin YS, Moxley JF, Stephanopoulos G (2005) Identifying gene targets for the metabolic engineering of lycopene biosynthesis in Escherichia coli. Metab Eng 7:155–164PubMedGoogle Scholar
  4. Andersson JO (2005) Lateral gene transfer in eukaryotes. Cell Mol Life Sci 62:1182–1197PubMedGoogle Scholar
  5. Arnold AE, Maynord Z, Gilbert G, Coley PD, Kursar TA (2000) Are tropical fungal endophytes hyperdiverse? Ecol Lett 3:167–274Google Scholar
  6. Asai M, Mizuta E, Izawa M, Haibara K, Kishi T (1978) Isolation, chemical characterization and structure of ansamitocin, a new antitumour antibiotic. Tetrahedron 35:1079–1085Google Scholar
  7. Bae GS et al (2010) Inhibition of lipopolysaccharide-induced inflammatory responses by piperine. Eur J Pharmacol 642:154–162PubMedGoogle Scholar
  8. Bano G, Amla V, Raina RK, Zutshi U, Chopra CL (1987) The effect of piperine on pharmacokinetics of phenytoin in healthy volunteers. Planta Med 53:568–569PubMedGoogle Scholar
  9. Bezerra DP et al (2008) In vitro and in vivo antitumor effect of 5-FU combined with piplartine and piperine. J Appl Toxicol 28:156–163PubMedGoogle Scholar
  10. Burdon JJ, Thrall PH (2009) Co-evolution of plants and their pathogens in natural habitats. Science 324:755–756PubMedGoogle Scholar
  11. Butterworth JH, Morgan ED (1968) Isolation of a substance that suppresses feeding in locusts. J Chem Soc Chem Commun 1968:23–24Google Scholar
  12. Butterworth JH, Morgan ED, Percy GR (1972) The structure of azadirachtin; the functional groups. J Chem Soc Perkin Trans 1:2445–2450Google Scholar
  13. Cassady JM, Chan KK, Floss HG, Leistner E (2004) Recent developments in the maytansinoids antitumour agents. Chem Pharm Bull 52:1–26PubMedGoogle Scholar
  14. Chandrashekhar RB, Jithan A, Narsimha RY, Malla RV (2008) Fabrication and investigations on hepatoprotective activity of sustained release biodegradable piperine microspheres. Int J Pharm Sci NanoTechnol 1:87–96Google Scholar
  15. Chonpathompikunlert P, Wattanathorn J, Muchimapura S (2010) Piperine, the main alkaloid of Thai black pepper, protects against neurodegeneration and cognitive impairment in animal model of cognitive deficit like condition of Alzheimer’s disease. Food Chem Toxicol 48:798–802PubMedGoogle Scholar
  16. Dahiya JS, Woods DL, Tiwari JP (1988) Piperine from an Ulocladium sp. Phytochemistry 27:2366Google Scholar
  17. DeJong JM, Liu Y, Bollon AP, Jennewein S, Williams D, Croteau R (2006) Genetic engineering of taxol biosynthetic genes in Saccharomyces cerevisiae. Biotechnol Bioeng 93:212–224PubMedGoogle Scholar
  18. Devkumar C, Kumar R (2008) Total synthesis of azadirachtin: a chemical odyssey. Curr Sci 95:573–575Google Scholar
  19. Dymowski W, Furmanowa M (1990) Investigating cytostatic substances in tissue of plants Maytenus molina in in vitro cultures. Chromatographic test of extracts from callus of Maytenus wallichiana. Acta Pol Pharm 47:51–54PubMedGoogle Scholar
  20. Engels B, Dahm P, Jennewein S (2008) Metabolic engineering of taxadiene biosynthesis in yeast as a first step towards Taxol (paclitaxel) production. Metab Eng 10:201–206PubMedGoogle Scholar
  21. Eyberger AL, Dondapati R, Porter JR (2006) Endophyte fungal isolates from Podophyllum peltatum produce podophyllotoxin. J Nat Prod 69:1121–1124PubMedGoogle Scholar
  22. Faeth SH, Hammon KE (1997) Fungal endophytes in oak tree; long term pattern of abundance and association with leaf miners. Ecology 78:810–819Google Scholar
  23. Fu M, Sun ZH, Zuo HC (2010) Neuroprotective effect of piperine on primarily cultured hippocampal neurons. Biol Pharm Bull 33:598–603PubMedGoogle Scholar
  24. Geylord ES, Preszler RW, Boecklen WJ (1996) Interactions between host plants, endophytic fungi, and a phytophagous insect in an Oak (Quercus grisea × Q. gambelii) hybrid zone. Oecologia 105:336–342Google Scholar
  25. Govindachari TR, Sandhya G, Raj SPG (1992a) Azadirachtin H and I: two new tetranortriterpenoid from Azadirachta indica. J Nat Prod 55:596–601Google Scholar
  26. Govindachari TR, Sandhya G, Raj SPG (1992b) Structure of azadirachtin K, a new tetranortriterpenoid from Azadirachta indica. Indian J Chem Sect B 31:295–298Google Scholar
  27. Govindachari TR, Gopalakrishnan G, Rajan SS, Kabaleeswaran V, Lessinger L (1996) Molecular and crystal structure of azadirachtin-H. Acta Crystallogr Sect B Struct Sci B52:145–150Google Scholar
  28. Govindachari TR, Gopalakrishnan G, Suresh G (1997) Purification of azadirachtin-B (3- tigloylazadirachtol) by preparative high performance liquid chromatography, using the recycling mode. J Liq Chromatogr Relat Technol 20:1633–1636Google Scholar
  29. Gunatilaka AAL (2006) Natural products from plant-associated microorganisms: distribution, structural diversity, bioactivity and implications of their occurrence. J Nat Prod 69:509–526PubMedGoogle Scholar
  30. Guo B, Wang Y, Sun X, Tang K (2008) Bioactive natural products from endophytes: a review. Appl Biochem Microbiol 44:136–142Google Scholar
  31. Hans J, Hause B, Strack D, Walter MH (2004) Cloning characterization and immunolocalization of a mycorrhizal inducible 1-Deoxy-D-Xylulose 5-phosphate reductoisomerase in arbuscule containing cells of Maize. Plant Physiol 134:614–624PubMedGoogle Scholar
  32. Higashide E, Asai M, Ootsu K, Tanida S, Kozay Y, Hasegawa T, Kishi T, Sugino Y, Yoneda M (1977) Ansamitocins, a group of novel maytansinoid antibiotics with anti-tumour properties from Nocardia. Nature 270:721–722PubMedGoogle Scholar
  33. Hines PJ, Zahn LM (2009) What’s bugging plants? Introduction to special issue. Science 324:741PubMedGoogle Scholar
  34. Hu RQ, Davies JA (1997) Effects of Piper nigrum L. on epileptiform activity in cortical wedges prepared from DBA/2 mice. Phytother Res 11:222–225Google Scholar
  35. Huang Q, Roessner CA, Croteau R, Scott AI (2001) Engineering Escherichia coli for the synthesis of taxadiene, a key intermediate in the biosynthesis of Taxol. Bioorg Med Chem 9:2237–2242PubMedGoogle Scholar
  36. Isaacs J (1994) Bush food aboriginal food and herbal medicine. Lansdowne Publishing Pty. Ltd., SydneyGoogle Scholar
  37. Jain R, Rivera MC, Moore JE, Lake JA (2003) Horizontal gene transfer accelerates genome innovation and evolution. Mol Biol Evol 20:1598–1602PubMedGoogle Scholar
  38. Jarvis AP, Morgan ED, van der Esch SA, Vitali F, Lay SV, Pape A (1997) Identification of azadirachtin in tissue-cultured cells of neem (A. indica). Nat Prod Lett 10:95–98Google Scholar
  39. Julsing MK, Koulman A, Woerdenbag HJ, Quax WJ, Kayser O (2006) Com-binatorial biosynthesis of medicinal plant secondary metabolites. Biomol Eng 23:265–279PubMedGoogle Scholar
  40. Kalinowski HO, Ermel K, Schmutterer H (1993) Strukturaufklärung eines azadirachtin derivates aus dem Marrangobaum Azadirachta excelsa durch NMR-spektroskopie. Liebigs Ann Chem 1993:1033–1035Google Scholar
  41. Kanokmedhakul S, Kanokmedhakul K, Prajuabsuk T, Panichajakul S, Panyamee P, Prabpai S, Kongsaeree P (2005) Azadirachtin derivatives from seed kernels of Azadirachta excelsa. J Nat Prod 68:1047–1050PubMedGoogle Scholar
  42. Karan RS, Bhargava VK, Garg SK (1988) Effect of piperine on the pharmacokinetic profile of isoniazid in rabbits. Indian J Pharmacol 30:254–256Google Scholar
  43. Kate KT, Laird SA (eds) (2000) The commercial use of biodiversity: access to genetic resources and benefit sharing. Earthscan Publications Ltd., LondonGoogle Scholar
  44. Kayser O, Quax WJ (eds) (2007) Medicinal plant biotechnology: from basic research to industrial applications. Wiley-VCH Verlag Gmbh & Co. KGaA, WeinheimGoogle Scholar
  45. Keeling PJ, Palmer JD (2008) Horizontal gene transfer in eukaryotic evolution. Nat Rev Genet 9:605–618PubMedGoogle Scholar
  46. Ketchum RE, Croteau R (1998) Recent progress toward an understanding of taxol biosynthesis in plant cell cultures. In: Ageta H, Aimi N, Ebizuka Y, Fujita T, Honda G (eds) Towards natural medicine research in the 21st century. Proceeding of the international symposium on natural medicines. Elsevier, Amsterdam, pp 339–348Google Scholar
  47. Ketchum RE, Gibson DM (1996) Paclitaxel production in suspension cell cultures of Taxus. Plant Cell Tissue Organ Cult 46:9–16Google Scholar
  48. Khajuria A, Thusus N, Zutshi U, Bedi KL (1997) Antioxidant potential of piperine on oxidant induced alterations in rat intestinal lumen. Indian Drugs 34:557–563Google Scholar
  49. Khosroushahi AY, Valizadeh M, Ghasempour A, Khosrowshahli M, Naghdibadi H, Dadpour MR, Omidi Y (2006) Improved taxol production by combination of inducing factors in suspension cell culture of Taxus baccata. Cell Biol Int 30:262–269PubMedGoogle Scholar
  50. Klenk A, Bokel M, Kraus W (1986) 3-tigloylazadirachtol (tigloyl = 2-methyl crotonoyl), an insect growth regulating constituent of Azadirachta indica. J Chem Soc Chem Commun 7:523–524Google Scholar
  51. Koepp AE, Hezari M, Zajicek J, Vogel BS, LaFever RE, Lewis NG, Croteau R (1995) Cyclization of geranylgeranyl diphosphate to taxa-4(5),11(12)-diene is the committed step of taxol biosynthesis in Pacific yew. J Biol Chem 270:8686–8690PubMedGoogle Scholar
  52. Koul IB, Kapil A (1993) Evaluation of the liver protective potential of piperine, an active principle of black and long peppers. Planta Med 59:413–417PubMedGoogle Scholar
  53. Kraus H, Bokel M, Klank A, Pohnl H (1985) The structure of azadirachtin and 22, 23-dihydro-23β-methoxyazadirachtin. Tetrahedron Lett 26:6435–6438Google Scholar
  54. Kraus W, Bokel M, Bruhn A, Cramer R, Klaiber I, Klenk A, Nagl G, Pohnl H, Sadlo H, Vogler B (1987) Structure determination by NMR of azadirachtin and related compounds from Azadirachta indica A. Juss. (Meliaceae). Tetrahedron 43:2817–2830Google Scholar
  55. Kupchan SM, Komoda Y, Court WA, Thomas GJ, Smith RM, Karim A, Gilmore CJ, Haltiwanger RC, Bryan RF (1972) Maytansine, a novel antileukaemic ansa macrolide from Maytenus ovatus. J Am Chem Soc 94:1355–1356Google Scholar
  56. Kusari S, Spiteller M (2011) Are we ready for industrial production of bioactive plant secondary metabolites utilizing endophytes? Nat Prod Rep 28:1203–1207PubMedGoogle Scholar
  57. Kusari S, Verma VC, Lamshöft M, Spiteller M (2012) An endophytic fungus from Azadirachta indica A. Juss. that produces azadirachtin. World J Microbiol Biotechnol 28:1287–1294PubMedGoogle Scholar
  58. Kutney JP, Beale MH, Salisbury PJ, Stuart KL, Worth BR, Townsley PM, Chalmers WT, Nilson K, Jacoli GG (1981) Isolation and characterization of natural products from plant tissue cultures of Maytenus buchananii. Phytochemistry 4:653–657Google Scholar
  59. Lautru S, Deeth RJ, Bailey LM, Challis GL (2005) Discovery of a new pep-tide natural product by Streptomyces coelicolor genome mining. Nat Chem Biol 1:265–269PubMedGoogle Scholar
  60. Lawrence JG, Roth JR (1996) Selfish operons: horizontal transfer may drive the evolution of gene clusters. Genetics 143:1843–1860PubMedGoogle Scholar
  61. Lee EB, Shin KH, Woo WS (1984) Pharmacological study on piperine. Arch Pharmacal Res 7:127–132Google Scholar
  62. Ley SV (1994) Synthesis and the chemistry of the insect anti-feedant azadirachtin. Pure Appl Chem 66:2099–2102Google Scholar
  63. Ley SV, Denholm AA, Wood A (1993) The chemistry of azadirachtin. Nat Prod Rep 10:109–157Google Scholar
  64. Li SM, Unsöld IA (2006) Post-genome research on the biosynthesis of ergot alkaloids. Planta Med 72:1117–1120PubMedGoogle Scholar
  65. Li S, Wang C, Wang M, Li W, Matsumoto K, Tang Y (2007) Antidepressant like effects of piperine in chronic mild stress treated mice and its possible mechanisms. Life Sci 80:1373–1381PubMedGoogle Scholar
  66. Li YC, Tao WY, Cheng L (2009) Paclitaxel production using co-culture of Taxus suspension cells and paclitaxel-producing endophytic fungi in a co-bioreactor. Appl Microbiol Biotechnol 83:233–239PubMedGoogle Scholar
  67. Lindahl AL, Olsson ME, Mercke P, Tollbom O, Schelin J, Brodelius M, Brodelius PE (2006) Production of the artemisin in precursor amorpha-4,11-diene by engineered Saccharomyces cerevisiae. Biotechnol Lett 28:571–580PubMedGoogle Scholar
  68. Luo X, Ma Y, Wu S, Wu D (1999) Two novel azadirachtin derivatives from Azadirachta indica. J Nat Prod 62:1022–1024PubMedGoogle Scholar
  69. Mordue AJ, Nisbet AJ (2000) Azadirachtin from the neem tree Azadirachta indica: its action against insects. An Soc Entomol Bras 29:615–632Google Scholar
  70. Mordue AJ, Simmonds MSJ, Ley SV, Blaney WM, Nasiruddin M, Nisbet AJ (1998) Actions of azadirachtin, a plant allelochemical against insects. Pestic Sci 54:277–284Google Scholar
  71. Morgan ED (2009) Azadirachtin: a scientific goldmine. Bioorg Med Chem 17:4096–4105PubMedGoogle Scholar
  72. Naill MC, Roberts SC (2005) Cell cycle analysis of Taxus suspension cultures at the single cell level as an indicator of culture heterogeneity. Biotechnol Bioeng 90:491–500PubMedGoogle Scholar
  73. Nims E, Dubois CP, Roberts SC, Walker EL (2006) Expression profiling of genes involved in paclitaxel biosynthesis for targeted metabolic engineering. Metab Eng 8:385–394PubMedGoogle Scholar
  74. Petrini O, Sieber TN, Toti L, Viret O (1992) Ecology, metabolite production, and substrate utilization in endophytic fungi. Nat Toxins 1:185–196PubMedGoogle Scholar
  75. Pie YQ (1983) A review of pharmacology and clinical use of piperine and its derivatives. Epilepsia 24:177–183Google Scholar
  76. Powel RG, Weisleder D, Smith CR, Kozlowski J, Rohwedder WK (1982) Treflorine, trenudine, and N-methyltrenudone: novel maytansinoids tumour inhibitors containing two fused macrocyclic rings. J Am Chem Soc 104:4929–4934Google Scholar
  77. Prakash UN, Srinivasan K (2010) Gastrointestinal protective effect of dietary spices during ethanol-induced oxidant stress in experimental rats. Appl Physiol Nutr Metab 35:134–141PubMedGoogle Scholar
  78. Prakash G, Bhojwani SS, Shrivastava AK (2002) Production of azadirachtin from tissue culture: state of the art and future prospects. Biotechnol Bioprocess Eng 7:185–193Google Scholar
  79. Pullen CB, Schmitz P, Hoffmann D, Meurer K, Boettcher T, von Bamberg D, Pereira AM, de Castro França S, Hauser M, Geertsema H, van Wyk A, Mahmud T, Floss HG, Leistner E (2003) Occurrence and non-detectability of maytansinoids in individual plants of the genera Maytenus and Putterlickia. Phytochemistry 62:377–387PubMedGoogle Scholar
  80. Puri SC, Verma V, Amna T, Qazi GN, Spiteller M (2005) An endophytic fungus from Nothapodytes foetida that produces camptothecin. J Nat Prod 68:1717–1719PubMedGoogle Scholar
  81. Puri SC, Nazir A, Chawla R, Arora R, Riyaz-ulHasan S, Amna T, Ahmed B, Verma V, Singh S, Sagar R, Sharma A, Kumar R, Sharma RK, Qazi GN (2006) The endophytic fungus Trametes hirsuta as a novel alternative source of podophyllotoxin and related aryl tetralin lignans. J Biotechnol 122:494–510PubMedGoogle Scholar
  82. Rafiq M, Dahot M (2010) Callus and azadirachtin related limnoids production through in vitro culture of neem (Azadirachta indica A. Juss). Afr J Biotechnol 9:449–453Google Scholar
  83. Ramaji N, Venkatakrishnan K, Madyastha KM (1996) 11-Epi- azadirachtin H from Azadirachta indica. Phytochemistry 42:561–562Google Scholar
  84. Rambold H (1988) Isomeric azadirachtin and their mode of action. In: Jacobson J (ed) Focus on phytochemical pesticides, vol 1, The neem tree. CRC Press, LondonGoogle Scholar
  85. Rembold H, Forster H, Sonnenbichler (1987) Z.Z. Naturforsch C, 42: 4–6Google Scholar
  86. Rinehart KL, Shield LS (1976) Chemistry of the ansamycin antibiotics. In: Herz W, Grisebach H, Kirby GW (eds) Progress in the chemistry of organic natural products. Springer, New York, pp 232–300Google Scholar
  87. Ro DK, Paradise EM, Ouellet M, Fisher KJ, Newman KL, Ndungu JM, Ho KA, Eachus RA, Ham TS, Kirby J, Chang MC, Withers ST, Shiba Y, Sarpong R, Keasling JD (2006) Production of the antimalarial drug pre-cursor artemisinic acid in engineered yeast. Nature 440:940–943PubMedGoogle Scholar
  88. Rosewich UL, Kistler HC (2000) Role of horizontal gene transfer in the evolution of fungi. Ann Rev Phytopathol 38:325–363Google Scholar
  89. Saikkonen K, Faeth SH, Helander ML, Sullivan TJ (1998) Fungal endophytes: a continuum of interactions with host plants. Ann Rev Ecol Syst 29:319–343Google Scholar
  90. Satdive RK, Fulzele DP, Eapen S (2007) Enhanced production of azadirachtin by hairy root cultures of Azadirachta indica A Juss. by elicitation and media optimization. J Biotechnol 128:281–289PubMedGoogle Scholar
  91. Schloss PD, Handelsman J (2005) Metagenomics for studying unculturable microorganisms: cutting the Gordian knot. Genome Biol 6:229–233PubMedGoogle Scholar
  92. Schmeer H, Jennewein S (2009) Bioorganic synthesis of the key taxoid pre-cursor taxa-4(5),11(12)-diene using a one-pot, two enzyme catalyzed re-actions. Enzyme Engineering XX, Groningen, the NetherlandsGoogle Scholar
  93. Schmidt EW, Nelson JT, Rasko DA, Sudek S, Eisen JA, Haygood MG, Ravel J (2005) Patellamide A and C biosynthesis by a microcin-like pathway in Prochloron didemni, the cyanobacterial symbiont of Lissoclinum patella. Proc Nat Acad Sci USA 102:7315–7320PubMedGoogle Scholar
  94. Shweta S, Zühlke S, Ramesha BT, Priti V, Kumar PM, Ravikanth G, Spiteller M, Vasudeva R, Shaanker RU (2010) Endophytic fungal strains of Fusarium solani, from Apodytes dimidiate E. Mey. ex Arn (Icacinaceae) produce camptothecin, 10-hydroxycamptothecin and 9-methoxycamptothecin. Phytochemistry 71:117–122PubMedGoogle Scholar
  95. Soliman SSM, Tsao R, Raizada MN (2011) Chemical inhibitors suggests endophytic fungal paclitaxel is derived from both mevalonate and non-mevalonate-like pathways. J Nat Prod 74:2497–2504PubMedGoogle Scholar
  96. Srinivasan K (2007) Black pepper and its pungent principle-piperine: a review of diverse physiological effects. Crit Rev Food Sci Nutr 47:735–748PubMedGoogle Scholar
  97. Staniek A, Woerdenbag HJ, Kayser O (2008) Endophytes: exploiting biodiversity for the improvement of natural product-based drug discovery. J Plant Interact 3:75–93Google Scholar
  98. Staniek A, Woerdenbag HJ, Kayser O (2009) Taxomyces andreanae: a presumed paclitaxel producer demystified? Planta Med 75:1561–1566PubMedGoogle Scholar
  99. Stephanopoulos G, Alper H, Moxley J (2004) Exploiting biological complexity for strain improvement through systems biology. Nat Biotechnol 22:1261–1267PubMedGoogle Scholar
  100. Stierle A, Strobel GA, Stierle D (1993) Taxol and taxane production by Taxomyces andreanae, an endophytic fungus of Pacific yew. Science 260:214–216PubMedGoogle Scholar
  101. Strobel GA (2002) Microbial gifts from the rain forest. Can J Plant Pathol 24:14–20Google Scholar
  102. Strobel GA, Daisy B, Castillo U, Harper J (2004) Natural products from endophytic fungi. J Nat Prod 67:257–268PubMedGoogle Scholar
  103. Takumi I, Mizuho I, Siho T, Yuzi I, Hideyuki Y (2008) Piperine, a pepper ingredient, improves the hepatic increase in free fatty acids caused by 2, 3, 7, 8- tetrachlorodibenzo-p-dioxin. J Health Sci 54:551–558Google Scholar
  104. Tan RX, Zou WX (2001) Endophytes: a rich source of functional metabolites. Nat Prod Rep 18:448–459PubMedGoogle Scholar
  105. Timmers L (1994) Herbal medicines used against epilepsy in developing countries; Publication Number PUG/94-4. Publicaties Wetenschapswinkel Geneesmiddelen, VrouwenGoogle Scholar
  106. Tyo KE, Alper HS, Stephanopoulos GN (2007) Expanding the metabolic engineering toolbox: more options to engineer cells. Trends Biotechnol 25:132–137PubMedGoogle Scholar
  107. Veitch GE, Beckmann E, Burke BJ, Boyer A, Ayats C, Ley SV (2007a) A relay route for the synthesis of azadirachtin. Angew Chem Int Ed 46:7633–7635Google Scholar
  108. Veitch GE, Beckmann E, Burke BJ, Boyer A, Ayats C, Ley SV (2007b) Synthesis of azadirachtin: a long but successful journey. Angew Chem Int Ed 46:7629–7632Google Scholar
  109. Veitch GE, Boyer A, Ley SV (2008) The azadirachtin story. Angew Chem Int Ed 47:9402–9429Google Scholar
  110. Verma VC, Kharwar RN, Strobel GA (2009) Chemical and functional diversity of natural products from plant associated endophytic fungi. Nat Prod Commun 4:1511–1532PubMedGoogle Scholar
  111. Verma VC, Lobkovsky E, Gange AC, Singh SK, Prakash S (2011) Piperine production by endophytic Periconia sp. isolated from Piper longum L. J Antibiot 64:427–431PubMedGoogle Scholar
  112. Vongpaseuth K, Roberts SC (2007) Advancements in the understanding of paclitaxel metabolism in tissue culture. Curr Pharm Biotechnol 8:219–236PubMedGoogle Scholar
  113. Walker K, Croteau R (2001) Taxol biosynthetic genes. Phytochemistry 58:1–7PubMedGoogle Scholar
  114. Walker K, Long R, Croteau R (2002) The final acylation step in taxol biosynthesis: cloning of the taxoid C13-side chain N-benzoyltransferase from Taxus. Proc Nat Acad Sci USA 99:9166–9171PubMedGoogle Scholar
  115. Wani MC, Taylor HL, Wall ME (1973) Plant antitumour agents: colubrinol acetate and colubrinol, antileukaemic ansa macrolides from Colubrina texensis. J Chem Soc Chem Commun 1973:390Google Scholar
  116. Wenzel SC, Gross F, Zhang Y, Fu J, Stewart F, Müller R (2005) Heterologous expression of a myxobacterial natural products assembly line in Pseudomonads via Red/ET recombineering. Chem Biol 12:349–356PubMedGoogle Scholar
  117. Weuster-Botzl D, Hekmat D, Puskeiler R, Franco-Lara E (2007) Enabling technologies: fermentation and downstream processing. Adv Biochem Eng Biotechnol 105:205–247Google Scholar
  118. Wildung MR, Croteau R (1996) A cDNA clone for taxadiene synthase, the diterpene cyclase that catalyzes the committed step of taxol biosynthesis. J Biol Chem 271:9201–9204PubMedGoogle Scholar
  119. Wu J, Lin L (2003) Enhancement of taxol production and release in Taxus chinensis cell cultures by ultrasound, methyl jasmonate and in situsol-vent extraction. Appl Microbiol Biotechnol 62:151–155PubMedGoogle Scholar
  120. Yu TW, Bai L, Clade D, Hoffmann D, Toelzer S, Trinh KQ, Xu J, Moss SJ, Leistner E, Floss HG (2002) The biosynthetic gene cluster of the maytansinoid antitumour agent ansamitocin from Actinosynnema pretiosum. Proc Nat Acad Sci USA 99:7968–7973PubMedGoogle Scholar
  121. Yukimune Y, Hara Y, Nomura E, Seto H, Yoshida S (2000) The configuration of methyl jasmonate affects paclitaxel and baccatin III production in Taxus cells. Phytochemistry 54:13–17PubMedGoogle Scholar
  122. Zazopoulos E, Huang K, Staffa A, Liu W, Bachmann BO, Nonaka K, Ahlert J, Thorson JS, Shen B, Farnet CM (2003) A genomics-guided approach for discovering and expressing cryptic metabolic pathways. Nat Biotechnol 21:187–190PubMedGoogle Scholar
  123. Zengler K, Walcher M, Clark G, Haller I, Toledo G, Holland T, Mathur EJ, Woodnutt G, Short J, Keller M (2005) High-throughput cultivation of microorganisms using microcapsules. Method Enzymol 397:124–130Google Scholar
  124. Zhang P, Zhou P, Jiang C, Yu H, Yu LJ (2008) Screening of taxol-producing fungi based on PCR amplification from Taxus. Biotechnol Lett 30:2119–2123PubMedGoogle Scholar
  125. Zhao J, Shan T, Mou Y, Zhao L (2011) Plant derived bioactive compounds produced by endophytic fungi. Mini Rev Med Chem 11:159–168PubMedGoogle Scholar
  126. 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. Prikl Biokhim Mikrobiol 43:490–494PubMedGoogle Scholar
  127. Zutshi RK, Singh R, Zutshi U, Johri RK, Atal CK (1985) Influence of piperine on rifampicin blood levels in patients of pulmonary tuberculosis. J Assoc Phys India 33:223–224Google Scholar

Copyright information

© Springer India 2014

Authors and Affiliations

  • Vijay Chandra Verma
    • 1
  • Satya Prakash
    • 2
  • Rana Gopal Singh
    • 3
  • Alan Christopher Gange
    • 4
  1. 1.Centre of Experimental Medicine and Surgery (CEMS), Institute of Medical SciencesBanaras Hindu UniversityVaranasiIndia
  2. 2.National Facility of Tribal and Herbal Medicine, Institute of Medical SciencesBanaras Hindu UniversityVaranasiIndia
  3. 3.Department of Nephrology, Institute of Medical SciencesBanaras Hindu UniversityVaranasiIndia
  4. 4.School of Biological SciencesRoyal Holloway University of LondonEgham, SurreyUK

Personalised recommendations