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Plant Cell, Tissue and Organ Culture (PCTOC)

, Volume 132, Issue 2, pp 239–265 | Cite as

Secondary metabolism of pharmaceuticals in the plant in vitro cultures: strategies, approaches, and limitations to achieving higher yield

  • Tasiu IsahEmail author
  • Shahid Umar
  • Abdul Mujib
  • Maheshwar Prasad Sharma
  • P. E. Rajasekharan
  • Nadia Zafar
  • Arajmand Frukh
Review

Abstract

Biotechnology is playing a vital alternative role in the production of pharmaceutical plant secondary metabolites to support industrial production and mitigate over-exploitation of natural sources. High-value pharmaceuticals that include alkaloids, flavonoids, terpenes, steroids, among others, are biosynthesized as a defensive strategy by plants in response to perturbations under natural environmental conditions. However, they can also be produced using plant cell, tissue, and organ culture techniques through the application of various in vitro approaches and strategies. In the past decades, efforts were on the clonal propagation, biomass and secondary metabolites production in the in vitro cultures of medicinally important plants that produce these molecules. In recent years, the effort has shifted towards optimizing culture conditions for their production through the application of cell line selection, elicitation, precursor feeding, two-phase co-culture among cell, tissue, and organ culture approaches. The efforts are made with the possibility to scale-up the production, meet pharmaceutical industry demand and conserve natural sources of the molecules. Applications of metabolic engineering and production from endophytes are also getting increasing attention but, the approaches are far from practical application in their industrial production.

Keywords

Medicinal plants Plant secondary metabolism Pharmaceuticals Natural products Bioactive compounds Elicitation 

Notes

Acknowledgements

Tasiu Isah is grateful to Hamdard University New Delhi, India for the support to his research work. Financial support provided by the Department of Biotechnology, Government of India New Delhi and The World Academy of Science for the Advancement of Science in the Developing World Trieste, Italy through DBT-TWAS Postgraduate Research Fellowship to Tasiu Isah is also acknowledged.

Author contributions

TI conceived the manuscript idea, designed the contents, contributed to a large extent in all sections of the manuscript, produced Table, figures and responsible for the final version of the manuscript, AM, and NZ partly contributed in the elicitation sections, SU and MPS assisted with editing, PER partly contributed in the camptothecin production section, AF partly contributed in the introduction section.

Compliance with ethical standards

Conflict of interest

The authors declare that no conflict of interest exists in the manuscript contents.

Supplementary material

11240_2017_1332_MOESM1_ESM.pdf (230 kb)
Supplementary material 1 (PDF 230 KB)
11240_2017_1332_MOESM2_ESM.pdf (484 kb)
Supplementary material 2 (PDF 484 KB)

References

  1. Abraham J, Thomas TD (2017) Hairy root culture for the production of useful secondary metabolites. In: Malik S (ed) Biotechnology & production of anti-cancer compounds, Springer, New York, pp 201–230CrossRefGoogle Scholar
  2. Abyari M, Nasr N, Soorni J, Sadhu D (2016) Enhanced accumulation of scopoletin in cell suspension culture of Spilanthes acmella Murr. using precursor feeding. Braz Arch Biol Technol 59:e16150533.  https://doi.org/10.1590/1678-4324-2016150533 CrossRefGoogle Scholar
  3. Ahmad S, Garg M, Tamboli ET, Abdin MZ, Ansari SH (2013) In vitro production of alkaloids: factors, approaches, challenges and prospects. Pharmacogn Rev 7(13):27PubMedPubMedCentralCrossRefGoogle Scholar
  4. Ali M, Isah T, Mujib A, Dipti (2016) Climber plants: medicinal importance and conservation strategies. In: Shahzad A, Sharma S, Siddiqui SA (eds) Biotechnological strategies for the conservation of medicinal and ornamental climbers, Springer, New York, pp 101–138CrossRefGoogle Scholar
  5. Alikaridis F, Papadakis D, Pantelia K, Kephalas T (2000) Flavonolignan production from Silybum marianum transformed and untransformed root cultures. Fitoterapia 71(4):379–384.  https://doi.org/10.1016/S0367-326X(00)00134-9 PubMedCrossRefGoogle Scholar
  6. Allen RS, Millgate AG, Chitty JA et al (2004) RNAi-mediated replacement of morphine with the nonnarcotic alkaloid reticuline in opium poppy. Nat Biotechnol 22(12):1559.  https://doi.org/10.1038/nbt1033 PubMedCrossRefGoogle Scholar
  7. Amna T, Puri SC, Verma V et al (2006) Bioreactor studies on the endophytic fungus Entrophospora infrequens for the production of an anticancer alkaloid camptothecin. Can J Microbiol 52(3):189–196.  https://doi.org/10.1139/w05-122 PubMedCrossRefGoogle Scholar
  8. 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(4):1476–1489.  https://doi.org/10.1590/S1517-838220120004000032 PubMedPubMedCentralCrossRefGoogle Scholar
  9. Andarwulan N, Shetty K (1999) Phenolic content in the differentiated tissue cultures of untransformed & Agrobacterium-transformed roots of anise (Pimpinella anisum L.). J Agric Food Chem 47(4):1776–1780PubMedCrossRefGoogle Scholar
  10. Angelova Z, Georgie S, Roos W (2006) Elicitation of plants. Biotechnol Biotechnol Eq 20(2):72–83.  https://doi.org/10.1080/13102818.2006.10817345 CrossRefGoogle Scholar
  11. Arora J, Roat C, Goyal S, Ramawat KG (2009) High stilbenes accumulation in root cultures of Cayratia trifolia (L.) domin grown in shake flasks. Acta Physiol Plant 31(6):1307.  https://doi.org/10.1007/s11738-009-0359-3 CrossRefGoogle Scholar
  12. Aryanti MB, Ermayanti TM, Mariska I (2001) Production of the antileukemic agent in untransformed and untransformed root cultures of Artemisia cina. Annales Bogorienses 8(1):11–16Google Scholar
  13. Baenas N, Garcia-Viguera C, Moreno DA (2014) Elicitation: a tool for enriching the bioactive composition of foods. Molecules 19:13541–13563.  https://doi.org/10.3390/molecules190913541 PubMedCrossRefGoogle Scholar
  14. Bairu MW, Aremu AO, van Staden J (2011) Somaclonal variation in plants: causes & detection methods. Plant Growth Regul 63:147–173.  https://doi.org/10.1007/s10725-010-9554-x CrossRefGoogle Scholar
  15. Baiza AM, Quiroz A, Ruiz JA, Maldonado-Mendoza I (1998) Growth patterns & alkaloid accumulation in hairy root & untransformed root cultures of Datura stramonium. Plant Cell Tiss Organ Cult 54(2):123–130.  https://doi.org/10.1023/A:1006110518548 CrossRefGoogle Scholar
  16. Beau J, Mahid N, Burda WN, et al. (2012) Epigenetic tailoring for the production of anti-infective cytosporones from the marine fungus Leucostoma persoonii. Mar Drug 10:762–774.  https://doi.org/10.3390/md10040762 CrossRefGoogle Scholar
  17. Bedi YS, Ogra RK-, Koul K, Kaul BL, Kapil RS (1996) Yew (Taxus spp.): a new look on utilization, cultivation, & conservation. In: Handa SS, Kaul MK (eds) Supplement to cultivation and utilization of medicinal plants, Regional Research Laboratory, Jammu-Tawi, pp 443–456Google Scholar
  18. Bentebibel S, Moyano E, Palazon J et al (2005) Effects of immobilization by entrapment in alginate & scale-up on paclitaxel & baccatin III production in cell suspension cultures of Taxus baccata. Biotechnol Bioeng 89(6):647–655.  https://doi.org/10.1002/bit.20321 PubMedCrossRefGoogle Scholar
  19. Bertaux J, Schmid M, Hutzler P et al (2005) Occurrence and distribution of endobacteria in the plant-associated mycelium of the ectomycorrhizal fungus Laccaria bicolor S238N. Environ Microbiol 7(11):1786–1795.  https://doi.org/10.1111/j.1462-2920.2005.00867.x PubMedCrossRefGoogle Scholar
  20. Bhadra R, Shanks JV (1997) Transient studies of nutrient uptake, growth, & indole alkaloid accumulation in heterotrophic cultures of hairy root of Catharanthus roseus. Biotechnol Bioeng 55(3):527–534.  https://doi.org/10.1002/(SICI)1097-0290 PubMedCrossRefGoogle Scholar
  21. Bhagwath SG, Hjortso MA (2000) Statistical analysis of elicitation strategies for thiarubrine A production in hairy root cultures of Ambrosia artemisiifolia. J Biotechnol 80(2):159–167.  https://doi.org/10.1016/S0168-1656(00)00256-X PubMedCrossRefGoogle Scholar
  22. Bhalkar BN, Patil SM, Govindwar SP (2016) Camptothecine production by mixed fermentation of two endophytic fungi from Nothapodytes nimmoniana. Fungal Biol 120(6):873–883.  https://doi.org/10.1016/j.funbio.2016.04.003 PubMedCrossRefGoogle Scholar
  23. Bharathi P, Philomina D (2010) Effect of nutritional factors and precursors on the formation of colchicine in Gloriosa superba in vitro. Res Biotechnol 1:29–37Google Scholar
  24. Bianciotto V, Bandi C, Minerdi D et al (1996) An obligately endosymbiotic mycorrhizal fungus itself harbors obligately intracellular bacteria. Appl Environ Microbiol 62(8):3005–3010PubMedPubMedCentralGoogle Scholar
  25. Bienaime C, Melin A, Bensaddek L et al (2015) Effects of plant growth regulators on cell growth & alkaloids production by cell cultures of Lycopodiella inundata. Plant Cell Tiss Organ Cult 123(3):523–533.  https://doi.org/10.1007/s11240-015-0856-6 CrossRefGoogle Scholar
  26. Bonfill M, Cusido RM, Palazon J, Pinol MT, Morales C (2002) Influence of auxins on organogenesis & ginsenoside production in Panax ginseng calluses. Plant Cell Tiss Organ Cult 68:73–78.  https://doi.org/10.1023/A:1012996116836 CrossRefGoogle Scholar
  27. Bonfill M, Exposito O, Moyano E et al (2006) Manipulation by culture mixing & elicitation of paclitaxel & baccatin III production in the Taxus baccata suspension cultures. In Vitro Cell Dev Biol-Plant 42(5):422–426.  https://doi.org/10.1079/IVP2006761 CrossRefGoogle Scholar
  28. Bouque V, Bourgaud F, Nguyen C-, Guckert A (1998) Production of daidzein by the callus cultures of Psoralea species & comparison with plants. Plant Cell Tiss Organ Cult 53(1):35–40.  https://doi.org/10.1023/A:1006057211490 CrossRefGoogle Scholar
  29. Bourgaud F, Gravot A, Milesi S, Gontier E (2001) Production of plant secondary metabolites: a historical perspective. Plant Sci 161(5):839–851.  https://doi.org/10.1016/S0168-9452(01)00490-3 CrossRefGoogle Scholar
  30. Brodelius P (1988) Permeabilization of plant cells for the release of intracellularly stored products: viability studies. Appl Microbiol Biotechnol 27:561–566.  https://doi.org/10.1007/BF00451632 CrossRefGoogle Scholar
  31. Cai Z, Kastell A, Knorr D, Smetanska I (2012a) Exudation: an expanding technique for continuous production & release of secondary metabolites from the plant cell suspension and hairy root cultures. Plant Cell Rep 31:461–477.  https://doi.org/10.1007/s00299-011-1165-0 PubMedCrossRefGoogle Scholar
  32. Cai Z, Knorr D, Smetanska I (2012b) Enhanced anthocyanins & resveratrol production in Vitis vinifera cell suspension culture by indanoyl-isoleucine, N-linolenoyl-l-glutamine, and insect saliva. Enzyme Microb Tech 50:29–34.  https://doi.org/10.1016/j.enzmictec.2011.09.001 CrossRefGoogle Scholar
  33. Chan W, Staba EJ (1965) Alkaloid production by Datura callus & suspension tissue cultures. Lloydia 28:55Google Scholar
  34. Chetri SK, Kapoor H, Agrawal V (2016) Marked enhancement of sennoside bioactive compounds through precursor feeding in Cassia angustifolia Vahl & cloning of isochorismate synthase gene involved in its biosynthesis. Plant Cell Tiss Organ Cult 124(2):431–446.  https://doi.org/10.1007/s11240-015-0905-1 CrossRefGoogle Scholar
  35. Choi HJ, Tao BY, Okos MR (1995) Enhancement of secondary metabolite production by immobilized Gossypium arboreum cells. Biotechnol Prog 11(3):306–311.  https://doi.org/10.1021/bp00033a011 CrossRefGoogle Scholar
  36. Choi SM, Son SH, Yun SR et al (2000) Pilot-scale culture of adventitious roots of ginseng in a bioreactor system. Plant Cell Tiss Organ Cult 62(3):187–193CrossRefGoogle Scholar
  37. Chokkathukalam A, Kim DH, Barrett MP, Breitling R, Creek DJ (2014) Stable isotope labeling studies in metabolomics: new insights into structure & dynamics of metabolic networks. Bioanal 6(4):511–524.  https://doi.org/10.4155/bio.13.348 CrossRefGoogle Scholar
  38. Constabel F, Kurz WGW (1999) Cell differentiation & secondary metabolite production. In: Soh WY, Bhojwani SS (eds) Morphogenesis in plant tissue cultures, Springer, New York, pp 463–501CrossRefGoogle Scholar
  39. Croteau R, Ketchum RE, Long RM, Kaspera R, Wildung MR (2006) Taxol biosynthesis and molecular genetics. Phytochem Rev 5(1):75–97.  https://doi.org/10.1007/s11101-005-3748-2 PubMedPubMedCentralCrossRefGoogle Scholar
  40. Cui XH, Chakrabarty D, Lee E-J, Paek KY (2010) Production of adventitious roots & secondary metabolites by Hypericum perforatum L. in a bioreactor. Biores Technol 101(12):4708–4716.  https://doi.org/10.1016/j.biortech.2010.01.115 CrossRefGoogle Scholar
  41. Cui XH, Murthy HN, Jin YX et al (2011) Production of adventitious root biomass & secondary metabolites of Hypericum perforatum L. in a balloon-type airlift reactor. Biores Technol 102(21):10072–10079CrossRefGoogle Scholar
  42. Cusido RM, Palazon J, Bonfill M et al (2002) Improved paclitaxel and baccatin III production in suspension cultures of Taxus media. Biotechnol Progr 18(3):418–423.  https://doi.org/10.1021/bp0101583 CrossRefGoogle Scholar
  43. Cusido RM, Onrubia M, Sabater-Jara AB et al (2014) A rational approach to improving the biotechnological production of the taxanes in plant cell cultures of Taxus spp. Biotechnol Adv 32(6):1157–1167PubMedCrossRefGoogle Scholar
  44. Dandin VS- Murthy HN (2012) Enhanced in vitro multiplication of Nothapodytes nimmoniana Graham using semi-solid & liquid cultures & estimation of camptothecin in the regenerated plants. Acta Physiol Plant 34:1381–1386.  https://doi.org/10.1007/s11738-012-0934-x CrossRefGoogle Scholar
  45. Davuluri GR, van Tuinen A, Fraser PD et al. (2005) Fruit-specific RNAi-mediated suppression of DET1 enhances carotenoid and flavonoid content in tomatoes. Nature Biotechnol.  https://doi.org/10.1038/nbt1108 Google Scholar
  46. Deepthi S, Satheeshkumar K (2016) Cell line selection combined with jasmonic acid elicitation enhance camptothecin production in the cell suspension culture of Ophiorrhiza mungos L. Applied Microbiol Biotechnol.  https://doi.org/10.1007/s00253-016-7808-x Google Scholar
  47. DiCosmo F, Misawa M (1995) Plant cell & tissue culture: alternatives for metabolite production. Biotechnol Adv 13:425–435.  https://doi.org/10.1016/0734-9750(95)02005-N PubMedCrossRefGoogle Scholar
  48. Dieuaide-Noubhani M, Alonso AP, Rolin D, Eisenreich W, Raymond P (2007) Metabolic flux analysis: recent advances in carbon metabolism in plants. In: Baginsky S, Fernie AR (eds) Plant systems biology, Birkhäuser Verlag, Basel, pp 213–243CrossRefGoogle Scholar
  49. Dixon RA (2001) Natural products and plant disease resistance. Nature 411(6839):843–847.  https://doi.org/10.1038/35081178 PubMedCrossRefGoogle Scholar
  50. Doran PM (2002) Properties and applications of hairy-root cultures. In: Plant biotechnology and transgenic plants. Mercel Dekker Inc, New York, pp 143–162Google Scholar
  51. Dornenburg H, Knorr D (1995) Strategies for improvement of secondary metabolite production in the plant cell cultures. Enzyme Microbial Technol 17(8):674–684.  https://doi.org/10.1016/0141-0229(94)00108-4 CrossRefGoogle Scholar
  52. Dudareva N, Andersson S, Orlova I, Gatto et al (2005) The non-mevalonate pathway supports both monoterpene and sesquiterpene formation in snapdragon flowers. Proc Nat Acad Sci USA 102(3):933–938.  https://doi.org/10.1073/pnas.0407360102 PubMedPubMedCentralCrossRefGoogle Scholar
  53. Facchini PJ, De Luca V (2008) Opium poppy and Madagascar periwinkle: model non-model systems to investigate alkaloid biosynthesis in plants. The Plant J 54(4):763–784.  https://doi.org/10.1111/j.1365-313X.2008.03438.x PubMedCrossRefGoogle Scholar
  54. Farre G, Blancquaert D, Capell T et al (2014) Engineering complex metabolic pathways in plants. Ann Rev Plant Biol 65:187–223.  https://doi.org/10.1146/annurev-arplant-050213-035825 CrossRefGoogle Scholar
  55. Fazal H, Abbasi BH, Ahmad N (2014) Optimization of adventitious root culture for the production of biomass & secondary metabolites in Prunella vulgaris L. Applied Biochem Biotechnol 174(6):2086–2095.  https://doi.org/10.1007/s12010-014-1190-x CrossRefGoogle Scholar
  56. Ferrie AM (2010) Protocols for in vitro cultures and secondary metabolite analysis of aromatic and medicinal plants. Ann Bot 105(4):vii–viiiPubMedCentralCrossRefGoogle Scholar
  57. Figueiro ADA, Correa CM, Astarita LV, Santarem ER (2010) Long-term maintenance of the in vitro cultures affects growth & secondary metabolism of St. John’s Wort. Ciencia Rural 40(10):2115–2121.  https://doi.org/10.1590/S0103-84782010001000010 CrossRefGoogle Scholar
  58. Filova A (2014) Production of secondary metabolites in the plant tissue cultures. Res J Agric Sci 46(1):236–245Google Scholar
  59. Flores HE (1987) Use of plant cells & organ culture in the production of biological chemicals. In: Flores HE (ed) ACS Symposium Series, vol 334. Oxford University Press, Oxford, pp 66–86Google Scholar
  60. Fulzele DP, Satdive RK, Pol BB (2002) Untransformed root cultures of Nothapodytes foetida & production of camptothecin. Plant Cell Tiss Organ Cult 69(3):285–288CrossRefGoogle Scholar
  61. Fulzele DP, Satdive R, Kamble S et al (2015) Improvement of anticancer drug camptothecin production by the gamma irradiation on callus cultures of Nothapodytes foetida. Int J Pharm Res Allied Sci 4(1):19–27Google Scholar
  62. Gandhi SG, Mahajan V, Bedi YS (2015) Changing trends in biotechnology of secondary metabolism in medicinal and aromatic plants. Planta 241(2):303–317.  https://doi.org/10.1007/s00425-014-2232-x PubMedCrossRefGoogle Scholar
  63. Gaosheng H, Jingming J (2012) Production of the useful secondary metabolites through the regulation of biosynthetic pathway in the cell & tissue suspension culture of medicinal plants. In: Gaosheng H, Jingming J (eds) Recent advances in plant in vitro culture. INTECH, RijekaGoogle Scholar
  64. Georgiev MI, Weber J (2014) Bioreactors for plant cells: hardware configuration and internal environment optimization as tools for wider commercialization. Biotechnol Lett 36(7):1359–1367.  https://doi.org/10.1007/s10529-014-1498-1 PubMedCrossRefGoogle Scholar
  65. Georgiev M, Pavlov A, Ilieva M (2006) Selection of high rosmarinic acid producing Lavandula vera MM cell lines. Process Biochem 41(9):2068–2071.  https://doi.org/10.1016/j.procbio.2006.05.007 CrossRefGoogle Scholar
  66. Gibson SI (2005) Control of plant development and gene expression by sugar signaling. Curr Opin Plant Biol 8:93–102.  https://doi.org/10.1016/j.pbi.2004.11.003 PubMedCrossRefGoogle Scholar
  67. Giri A, Narasu ML (2000a) Production of podophyllotoxin from Podophyllum hexandrum: a potential natural product for clinically useful anticancer drugs. Cytotechnol 34(1–2):17–26.  https://doi.org/10.1023/A:1008138230896 CrossRefGoogle Scholar
  68. Giri A, Narasu M (2000b) Transgenic hairy roots: recent trends & application. Biotechnol Adv 18:1–22.  https://doi.org/10.1016/S0734-9750(99)00016-6 PubMedCrossRefGoogle Scholar
  69. Giri CC, Zaheer M (2016) Chemical elicitors versus secondary metabolite production the in vitro using plant cell, tissue & organ cultures: recent trends and a sky eye view appraisal. Plant Cell Tiss Organ Cult 126:1–18.  https://doi.org/10.1007/s11240-016-0985-6 CrossRefGoogle Scholar
  70. Greger H (2017) Phytocarbazoles: alkaloids with great structural diversity and pronounced biological activities. Phytochem Rev.  https://doi.org/10.1007/s11101-017-9521-5 Google Scholar
  71. Guardiola J, Iborra JL, Canovas M (1995) A model that links growth and secondary metabolite production in plant cell suspension cultures. Biotechnol Bioeng 46(3):291–297.  https://doi.org/10.1002/bit.260460313 PubMedCrossRefGoogle Scholar
  72. Gupta K, Garg S, Singh J, Kumar M (2014) Enhanced production of naphthoquinone metabolite (shikonin) from the cell suspension culture of Arnebia sp. & its up-scaling through bioreactor. 3 Biotech 4(3):263–273.  https://doi.org/10.1007/s13205-013-0149-x PubMedCrossRefGoogle Scholar
  73. Gurudatt PS, Priti V, Shweta S- et al (2010) Attenuation of camptothecin production and a negative relation between the hyphal biomass and camptothecin content in endophytic fungal strains isolated from Nothapodytes nimmoniana Grahm (Icacinaceae). Curr Sci 98(8):1006–1010Google Scholar
  74. Hashimoto T, Yun DJ, Yamada Y (1993) Production of tropane alkaloids in genetically engineered root cultures. Pyhtochem 32:713–718.  https://doi.org/10.1016/S0031-9422(00)95159-8 CrossRefGoogle Scholar
  75. Heinig U, Scholz S, Jennewein S (2013) Getting to the bottom of taxol biosynthesis by fungi. Fungal Div 60:161–170.  https://doi.org/10.1007/s13225-013-0228-7 CrossRefGoogle Scholar
  76. Herbert RB (1989) The biosynthesis of secondary metabolites: techniques for biosynthesis, Springer, New York, pp 15–20CrossRefGoogle Scholar
  77. Hibino K, Ushiyama K (1999) Commercial production of ginseng by the plant tissue culture technology. In: Fu TJ, Singh G, Curtis WR (eds) Plant cell & tissue culture for production of food ingredients, Springer, New York, pp 215–224CrossRefGoogle Scholar
  78. Higashi Y, Saito K (2013) Network analysis for gene discovery in plant-specialized metabolism. Plant Cell Environ 36(9):1597–1606.  https://doi.org/10.1111/pce.12069 PubMedCrossRefGoogle Scholar
  79. Hitaka Y, Kino-Oka M, Taya M, Tone S (1997) Effect of liquid flow on culture of red beet hairy roots in single column reactor. J Chem Eng Jpn 30(6):1070–1075.  https://doi.org/10.1252/jcej.30.1070 CrossRefGoogle Scholar
  80. Hoffman MT, Arnold AE (2010) Diverse bacteria inhabit living hyphae of phylogenetically diverse fungal endophytes. Appl Environ Microbiol 76(12):4063–4075.  https://doi.org/10.1128/AEM.02928-09 PubMedPubMedCentralCrossRefGoogle Scholar
  81. Hu ZB, Du M (2006) Hairy root & its application in plant genetic engineering. J Integr Plant Biol 48(2):121–127.  https://doi.org/10.1111/j.1744-7909.2006.00121.x CrossRefGoogle Scholar
  82. Hussain MS, Fareed S, Ansari S et al (2012) Current approaches toward the production of plant secondary metabolites. J Pharm BioAllied Sci 4:10–20.  https://doi.org/10.4103/0975-7406.92725 PubMedPubMedCentralCrossRefGoogle Scholar
  83. Isah T (2015a) Natural sources of taxol. Br J Pharm Res 6(4):214–227.  https://doi.org/10.9734/BJPR/2015/16293 CrossRefGoogle Scholar
  84. Isah T (2015b) Adjustments to in vitro culture conditions and associated anomalies in plants. Acta Biol Cracov Bot 57(2):9–28.  https://doi.org/10.1515/abcsb-2015-0026 Google Scholar
  85. Isah T (2015c) Rethinking Ginkgo biloba L.: medicinal uses and conservation. Pharmacogn Rev 9(18):140.  https://doi.org/10.4103/0973-7847.162137 PubMedPubMedCentralCrossRefGoogle Scholar
  86. Isah T (2016) Anti-cancer alkaloids from trees: development into drugs. Pharmacogn Rev 10(20):90.  https://doi.org/10.4103/0973-7847.194047 PubMedPubMedCentralCrossRefGoogle Scholar
  87. Isah T (2017) Production of camptothecin in the elicited callus cultures of Nothapodytes nimmoniana (J.Graham) mabberly. Chem Pap 71(6):1091–1106.  https://doi.org/10.1007/s11696-016-0056-9 CrossRefGoogle Scholar
  88. Isah T, Mujib A (2015a) In vitro propagation & camptothecin production in Nothapodytes nimmoniana. Plant Cell Tiss Organ Cult 121:1–10.  https://doi.org/10.1007/s11240-014-0683-1 CrossRefGoogle Scholar
  89. Isah T, Mujib A (2015b) Camptothecin from Nothapodytes nimmoniana: a review on biotechnology applications. Acta Physiol Plant 37:106.  https://doi.org/10.1007/s11738-015-1854-3 CrossRefGoogle Scholar
  90. Jackson P, Attalla MI (2010) N-Nitrosopiperazines form at high pH in post-combustion capture solutions containing piperazine: a low-energy collisional behavior study. Rapid Commun Mass Spectrom 24(24):3567–3577.  https://doi.org/10.1002/rcm PubMedCrossRefGoogle Scholar
  91. Jaisi A, Panichayupakaranant P (2016) Enhanced plumbagin production in Plumbago indica root cultures by l-alanine feeding and in situ adsorption. Plant Cell Tiss Organ Cult 38(2):351–355.  https://doi.org/10.1007/s11240-016-1155-6 Google Scholar
  92. Jang HR, Lee HJ, Park BJ et al (2016a) Establishment of embryogenic cultures and determination of their bioactive properties in Rosa rugosa. Hortic Environ Biotechnol 57(3):291–298.  https://doi.org/10.1007/s13580-016-0012-1 CrossRefGoogle Scholar
  93. Jang HR, Lee HJ, Shohael AM et al (2016b) Production of biomass and bioactive compounds from shoot cultures of Rosa rugosa using a bioreactor culture system. Hortic Environ Biotechnol 57(1):79–87.  https://doi.org/10.1007/s13580-016-0111-z CrossRefGoogle Scholar
  94. Janick J, Whipkey A, Kitto SL, Frett J (1994) Micropropagation of Cephalotaxus harringtonia. HortSci 29(2):120–122Google Scholar
  95. Jeandet P, Clement C, Tisserant LP, Crouzet J, Courot E (2016) Use of grapevine cell cultures for the production of phytostilbenes of cosmetic interest. CR Chim 19(9):1062–1070.  https://doi.org/10.1016/j.crci.2016.02.013 CrossRefGoogle Scholar
  96. Jeong G, Park D, Hwang B, Park K, Kim S, Woo J (2002) Studies on mass production of transformed Panax ginseng hairy roots in bioreactor. Appl Biochem Biotech 98–100:1115–1127CrossRefGoogle Scholar
  97. Jeong JH, Jung SJ, Murthy HN et al (2005) Production of eleutherosides in in vitro regenerated embryos and plantlets of Eleutherococcus chiisanensis. Biotechnol Lett 27(10):701–704.  https://doi.org/10.1007/s10529-005-4693-2 PubMedCrossRefGoogle Scholar
  98. Jeong JH, Kim YS, Moon HK, Hwang SJ, Choi YE (2009) Effects of LED on growth, morphogenesis and eleutheroside contents of in vitro cultured plantlets of Eleutherococcus senticosus Maxim. Korean J Med Crop Sci 17(1):39–45Google Scholar
  99. Jeong YJ, Woo SG, An CH et al (2015) Metabolic engineering for resveratrol derivative biosynthesis in Escherichia coli. Mol Cells 38(4):318–326.  https://doi.org/10.14348/molcells.2015.2188 PubMedPubMedCentralCrossRefGoogle Scholar
  100. Jha S, Bandyopadhyay M, Chaudhuri KN, Ghosh S, Ghosh B (2005) Biotechnological approaches for the production of forskolin, withanolides, colchicine and tylophorine. Plant Genet Res 3(2):101–115.  https://doi.org/10.1079/PGR200571 CrossRefGoogle Scholar
  101. Jimenez-Garcia SN, Vazquez-Cruz MA, Guevara-Gonzalez RG et al (2013) Current approaches for the enhanced expression of the secondary metabolites as bioactive compounds in plants for agronomic & human health purposes-review. Pol J Food Nutri Sci 63(2):67–78.  https://doi.org/10.2478/v10222-012-0072-6 Google Scholar
  102. Kai G, Teng X, Cui L et al (2014) Effect of three plant hormone elicitors on the camptothecin accumulation and gene transcript profiling in Camptotheca acuminata seedlings. Intl J Sci 3(1):86–95Google Scholar
  103. 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(3):525–539.  https://doi.org/10.1007/s11101-015-9405-5 CrossRefGoogle Scholar
  104. 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(3):357–369.  https://doi.org/10.1007/s11816-012-0270-z CrossRefGoogle Scholar
  105. Karppinen K, Hokkanen J, Tolonen A, Maltila S, Hohtola A (2007) Biosynthesis of hyperforin & adhyperforin from amino acid precursors in the shoot cultures of Hypericum perforatum. Phytochem 68:1038–1045.  https://doi.org/10.1016/j.phytochem.2007.01.001 CrossRefGoogle Scholar
  106. Karuppusamy S (2009) A review on trends in production of secondary metabolites from higher plants by in vitro tissue, organ and cell cultures. J Med Plants Res 3(13):1222–1239Google Scholar
  107. Khelifi L, Zarouri B, Amdoun R et al (2011) Effects of elicitation and permeabilization on hyoscyamine content in Datura stramonium hairy roots. Adv Environ Biol 5:329–334Google Scholar
  108. Kim BJ, Gibson DM, Shuler ML (2004) Effect of sub culture & elicitation on the instability of taxol production in Taxus sp. suspension cultures. Biotechnol Prog 20(6):1666–1673.  https://doi.org/10.1021/bp034274c PubMedCrossRefGoogle Scholar
  109. Kintzios S (2008) Secondary metabolite production from plant cell cultures: the success stories of rosmarinic acid and taxol. In: Ramawat K, Merillon S (eds) Bioactive molecules and medicinal plants. Springer, Berlin, pp 85–100CrossRefGoogle Scholar
  110. Kiong AL, Mahmood M, Fodzillan NM, Daud SK (2005) Effects of precursor supplementation on the production of triterpenes by Centella asiatica callus culture. Pak J Biol Sci 8:1160–1169.  https://doi.org/10.3923/pjbs.2005.1160.1169 CrossRefGoogle Scholar
  111. Kolewe M (2011) development of plant cell culture processes to produce natural product pharmaceuticals: characterization, analysis, and modeling of plant cell aggregation. A Ph.D. Thesis submitted-to the Department of Chemical Engineering, Graduate school, University of Massachusetts Amherst, in partial fulfillment of requirements for the Degree of Doctor of Philosophy, pp 1–140Google Scholar
  112. Komaraiah P, Kishor PK, Carlsson M, Magnusson KE, Mandenius CF (2005) Enhancement of anthraquinone accumulation in Morinda citrifolia suspension cultures. Plant Sci 168(5):1337–1344.  https://doi.org/10.1016/j.plantsci.2005.01.017 CrossRefGoogle Scholar
  113. Kumara PM, Shweta S, Vasanthakumari MM et al. (2014) Endophytes and plant secondary metabolite synthesis: molecular and evolutionary perspective. In: Verma VC, Gange AC (eds) Advances in the endophytic research, Springer, New York, pp 177–190CrossRefGoogle Scholar
  114. Kusari S, Zuuhlke S, Spiteller M (2009a) An endophytic fungus from Camptotheca acuminata that produces camptothecin and analogues. J Nat Prod 72(1):2–7.  https://doi.org/10.1021/np800455b PubMedCrossRefGoogle Scholar
  115. Kusari S, Zuhlke S, Kosuth J, Cellarova E, Spiteller M (2009b) Light-independent metabolomics of endophytic Thielavia subthermophila provides insight into microbial hypericin biosynthesis. J Nat Prod 72(10):1825–1835.  https://doi.org/10.1021/np9002977 PubMedCrossRefGoogle Scholar
  116. Kusari S, Zuhlke S, Spiteller M (2011a) 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):764–775.  https://doi.org/10.1021/np1008398 PubMedCrossRefGoogle Scholar
  117. Kusari S, Hertweck C, Spiteller M (2012) Chemical ecology of endophytic fungi: origins of secondary metabolites. Chem Biol 19(7):792–798.  https://doi.org/10.1016/j.chembiol.2012.06.004 PubMedCrossRefGoogle Scholar
  118. Kusari S, Singh S, Jayabaskaran C (2014) Rethinking production of Taxol®(paclitaxel) using endophyte biotechnology. Trends Biotechnol 32(6):304–311.  https://doi.org/10.1016/j.tibtech.2014.03.011 PubMedCrossRefGoogle Scholar
  119. Kutchan T (1995) Alkaloid biosynthesis: the basis for metabolic engineering of medicinal plants. Plant Cell 7:1059–1070.  https://doi.org/10.1105/tpc.7.7.1059 PubMedPubMedCentralGoogle Scholar
  120. Lee MH, Cheng JJ, Lin CY, Chen YJ, Lu MK (2007a) Precursor-feeding strategy for production of solanine, solanidine, & solasodine by a cell culture of Solanum lyratum. Process Biochem 42(5):899–903.  https://doi.org/10.1016/j.procbio.2007.01.010 CrossRefGoogle Scholar
  121. Lee KJ, Park Y, Kim JY et al (2015) Production of biomass and bioactive compounds from adventitious root cultures of Polygonum multiflorum using air-lift bioreactors. J Plant Biotechnol 42(1):34–42.  https://doi.org/10.5010/JPB.2015.42.1.34 CrossRefGoogle Scholar
  122. Lee HJ, Kim YE, Yoon YJ et al (2016) Highly endoreduplicated floral organs of somaclonal variants in clonally propagated Phalaenopsis ‘Spring Dancer.’. Plant Cell Tiss Organ Cult 126(1):67–77.  https://doi.org/10.1007/s11240-016-0977-6 CrossRefGoogle Scholar
  123. Lu Y, Wang H, Wang W et al (2009) Molecular characterization and expression analysis of a new cDNA encoding strictosidine synthase from Ophiorrhiza japonica. Mol Biol Rep 36(7):1845–1852.  https://doi.org/10.1007/s11033-008-9389-y PubMedCrossRefGoogle Scholar
  124. Lu X, Tang K, Li P (2016) Plant metabolic engineering strategies for the production of pharmaceutical terpenoids. Front Plant Sci.  https://doi.org/10.3389/fpls.2016.01647 Google Scholar
  125. Mahmoud SS, Croteau RB (2001) Metabolic engineering of essential oil yield and composition in mint by altering expression of deoxyxylulose phosphate reductoisomerase and menthofuran synthase. Proc Nat Acad Sci 98(15):8915–8920.  https://doi.org/10.1073/pnas.141237298 PubMedPubMedCentralCrossRefGoogle Scholar
  126. Majerus F, Pareilleus A (1986) Production of indole alkaloids by gel-entrapped cells of Catharanthus roseus cells in a continuous flow reactor. Biotech Lett 8:863–866.  https://doi.org/10.1007/BF01078646 CrossRefGoogle Scholar
  127. Malik SS, Laura JS (2014) Distribution of camptothecin through plant kingdom. Int J Curr Res 6(5):6497–6507Google Scholar
  128. Malik S, Cusido RM, Mirjalili MH et al (2011a) Production of the anticancer drug taxol in Taxus baccata suspension cultures: a review. Process Biochem 46(1):23–34.  https://doi.org/10.1016/j.procbio.2010.09.004 CrossRefGoogle Scholar
  129. Malik S, Mirjalili MH, Fett-Neto AG, Mazzafera P, Bonfill M (2013) Living between two worlds: two-phase culture systems for producing plant secondary metabolites. Crit Rev Biotechnol 33(1):1–22.  https://doi.org/10.3109/07388551.2012.659173 PubMedCrossRefGoogle Scholar
  130. Mishra BN, Ranjan R (2008) Growth of hairy-root cultures in various bioreactors for the production of secondary metabolites. Biotechnol Appl Biochem 49(1):1–10.  https://doi.org/10.1042/BA20070103 PubMedCrossRefGoogle Scholar
  131. Mujib A, Ali M, Isah T, Dipti (2014) Somatic embryo mediated mass production of Catharanthus roseus in culture vessel (bioreactor): a comparative study. Saudi J Biol Sci 21(5):442–449.  https://doi.org/10.1016/j.sjbs.2014.05.007 PubMedPubMedCentralCrossRefGoogle Scholar
  132. Mukundan U, Bhide V, Singh G, Curtis WR (1998) pH-mediated release of betalains from transformed root cultures of Beta vulgaris. Appl Microbiol Biotechnol 50:241–245.  https://doi.org/10.1007/s002530051283 CrossRefGoogle Scholar
  133. Murashige T, Skoog F (1962) A revised medium for rapid growth and bioassays with tobacco tissue cultures. Physiol Plant 15:473–497.  https://doi.org/10.1111/j.1399-3054.1962.tb08052.x CrossRefGoogle Scholar
  134. Murthy HN, Hahn EJ, Paek KY (2008a) Adventitious roots and secondary metabolism. Chin J Biotechnol 24(5):711–716CrossRefGoogle Scholar
  135. Murthy HN, Lee EJ, Paek KY (2014a) Production of secondary metabolites from cell & organ cultures: strategies & approaches for biomass improvement & metabolite acumulation. Plant Cell Tiss Organ Cult 118(1):1–16.  https://doi.org/10.1007/s11240-014-0467-7 CrossRefGoogle Scholar
  136. Nagella P, Murthy HN (2010) Establishment of cell suspension cultures of Withania somnifera for production of withanolide A. Bioresour Technol 101(17):6735–6739.  https://doi.org/10.1016/j.biortech.2010.03.078 PubMedCrossRefGoogle Scholar
  137. Nagella P, Hosakatte NM, Ravishankar KV, Hahn EJ, Paek KY (2008) Analysis of genetic diversity among Indian niger [Guizotia abyssinica (L. f.) Cass.] cultivars based on randomly amplified polymorphic DNA markers. Electron J Biotechnol 11(1):140–144.  https://doi.org/10.2225/vol11-issue1-fulltext-14 CrossRefGoogle Scholar
  138. Naik PM, Manohar SH, Praveen N, Murthy HN (2010) Effects of sucrose & pH levels on the in vitro shoot regeneration from the leaf explants of Bacopa monnieri and accumulation of bacoside A in regenerated shoots. Plant Cell Tiss Organ Cult 100(2):235–239.  https://doi.org/10.1007/s11240-009-9639-2 CrossRefGoogle Scholar
  139. Namdeo AG, Jadhav TS, Rai PK, Gavali S, Mahadik KR (2007) Precursor feeding for enhanced production of secondary metabolites: a review. Pharmacogn Rev 1(2):227Google Scholar
  140. Nanda S, Mohanty JN, Mishra R, Joshi RK (2016) Metabolic engineering of phenyl propanoids in plants. In: Jha S (ed) Transgenesis and secondary metabolism: part of the series reference series in phytochemistry, Springer, New York, pp 1–26Google Scholar
  141. Neelwarne B, Thimmaraju R (2009) Bioreactor for cultivation of red beet hairy roots and in situ recovery of primary and secondary metabolites. Eng Life Sci 9(3):227–238.  https://doi.org/10.1002/elsc.200800116 CrossRefGoogle Scholar
  142. Newman DJ, Cragg GM (2016) Natural products as sources of new drugs from 1981 to 2014. J Nat Prod 79(3):629–661.  https://doi.org/10.1021/acs.jnatprod.5b01055 PubMedCrossRefGoogle Scholar
  143. O’Connor SE (2015) Engineering of secondary metabolism. Ann Rev Genet 49:71–94.  https://doi.org/10.1146/annurev-genet-120213-092053 PubMedCrossRefGoogle Scholar
  144. Oksman-Caldentey KM, Arroo R (2000) Regulation of tropane alkaloid metabolism in plants and plant cell cultures. In: Verpoorte R, Alfermann AW (eds) Metabolic engineering of plant secondary metabolism, Springer, New York, pp 253–281CrossRefGoogle Scholar
  145. Oksman-Caldentey KM, Inze D (2004) Plant cell factories in the post-genomic era: new ways to produce designer secondary metabolites. Trends Plant Sci 9(9):433–440.  https://doi.org/10.1016/j.tplants.2004.07.006 PubMedCrossRefGoogle Scholar
  146. Olszowska O, Alfermann AW, Furmanowa M (1996) Eugenol from normal & transformed root cultures of Coluria geoides. Plant Cell Tiss Organ Cult 45(3):273–276.  https://doi.org/10.1007/BF00043642 CrossRefGoogle Scholar
  147. Padmanabha BV, Chandrashekar M, Ramesha BT et al (2006) Patterns of accumulation of camptothecin, an anticancer alkaloid in Nothapodytes nimmoniana Graham., in Western Ghats, India: implications for the identifying high-yielding sources of the alkaloid. Curr Sci 90(1):95Google Scholar
  148. Palazon J, Pinol MT, Cusido RM, Morales C, Bonfill M (1997) Application of transformed root technology to production of bioactive metabolites. Recent Res Dev Plant Physiol 1:125–143Google Scholar
  149. Pandiangan D, Tilaar W, Nainggolan N, Wahyudi L (2013) Relations between catharanthine content enhancement with other associated secondary metabolites in Catharanthus roseus cell culture that treated tryptophan. Intl J Sci Res 4(1):2208–2212Google Scholar
  150. Park SY, Paek KY (2006) Endoreduplication pattern of somatic embryos and variants occurrence affected by pre-existed endoreduplicated cells in Doritaenopsis. J Plant Biotechnol 33(4):297–302CrossRefGoogle Scholar
  151. Park SY, Paek KY (2014) Bioreactor culture of shoots and somatic embryos of medicinal plants for production of bioactive compounds. In: Paek KY, Murthy HN, Zhong JJ (eds) Production of biomass and bioactive compounds using bioreactor technology, Springer, New York, pp 337–368Google Scholar
  152. Park SY, Murthy HN, Paek KY (2002) Rapid propagation of Phalaenopsis from floral stalk-derived leaves. In Vitro Cell Dev Biol-Plant 38(2):168–172.  https://doi.org/10.1079/IVP2001274 CrossRefGoogle Scholar
  153. Park SY, Cho HM, Moon HK, Kim YW, Paek KY (2011) Genotypic variation and aging effects on the embryogenic capability of Kalopanax septemlobus. Plant Cell Tiss Organ Cult 105(2):265–270.  https://doi.org/10.1007/s11240-010-9862-x CrossRefGoogle Scholar
  154. Patil RA, Kolewe ME, Roberts SC (2013a) Cellular aggregation is a key parameter associated with the long term variability in paclitaxel accumulation in suspension cultures. Plant Cell Tiss Organ Cult 112(3):303–310.  https://doi.org/10.1007/s11240-012-0237-3 CrossRefGoogle Scholar
  155. Paz TA, dos Santos VAFFM, Inacio MC et al (2017) Proteome profiling reveals insights into secondary metabolism in Maytenus ilicifolia (Celastraceae) cell cultures producing quinone methide triterpenes. Plant Cell Tiss Organ Cult 130:255–263.  https://doi.org/10.1007/s11240-017-1236-1 CrossRefGoogle Scholar
  156. Petrovska BB (2012) Historical review of medicinal plants’ usage. Pharmacogn Rev 6(11):1.  https://doi.org/10.4103/0973-7847.95849 PubMedPubMedCentralCrossRefGoogle Scholar
  157. Phyton Biotech (2014) Capacity, reliability and quality in taxane API supply. https://phytonbiotech.com/apis/docetaxel/. Accessed 8 Aug 2014
  158. Pohlscheidt M, Charaniya S, Bork C et al. (2013) Bioprocess and fermentation monitoring. Encycl Ind Biotechnol.  https://doi.org/10.1002/9780470054581.eib606.pub2 Google Scholar
  159. Poulter CD, Wiggins PL, Le AT (1981) Farnesylpyrophosphate synthetase. A stepwise mechanism for the 1′-4 condensation reaction. J Am Chem Soc 103(13):3926–3927.  https://doi.org/10.1021/ja00403a054 CrossRefGoogle Scholar
  160. Prakash L, Middha SK, Mohanty SK, Swamy MK (2016) Micropropagation and validation of genetic and biochemical fidelity among regenerates of Nothapodytes nimmoniana (Graham) Mabb. employing ISSR markers and HPLC. 3 Biotech 6(2):171.  https://doi.org/10.1007/s13205-016-0490-y PubMedPubMedCentralCrossRefGoogle Scholar
  161. Priti V, Ramesha BT, Singh S et al (2009) How promising are endophytic fungi as alternative sources of plant secondary metabolites? Curr Sci 97(4):477–478Google Scholar
  162. Pu X, Qu X, Chen F, Bao J, Zhang G, Luo Y (2013) Camptothecin-producing endophytic fungus Trichoderma atroviride LY357: isolation, identification, and fermentation conditions optimization for camptothecin production. Appl Microbiol Biotechnol 97(21):9365–9375.  https://doi.org/10.1007/s00253-013-5163-8 PubMedCrossRefGoogle Scholar
  163. 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):1717–1719.  https://doi.org/10.1021/np0502802 PubMedCrossRefGoogle Scholar
  164. Raghavendra S, Ramesh CK, Kumar V, Moinuddin Khan MH (2011) Elicitors and precursor induced effect on l-Dopa production in suspension cultures of Mucuna pruriens L. Front Life Sci 5(3–4):127–133.  https://doi.org/10.1080/21553769.2011.649188 CrossRefGoogle Scholar
  165. Rahimi S, Hasanloo T, Najafi F, Khavari-Nejad RA (2011) Enhancement of silymarin accumulation using precursor feeding in Silybum marianum hairy root cultures. Plant Omics J 4(1):34–39Google Scholar
  166. Raj D, Kokotkiewicz A, Drys A, Luczkiewicz M (2015a) Effect of plant growth regulators on the accumulation of indolizidine alkaloids in Securinega suffruticosa callus cultures. Plant Cell Tiss Organ Cult 123(1):39–45.  https://doi.org/10.1007/s11240-015-0811-6 CrossRefGoogle Scholar
  167. Ramachandra SR, Ravishankar GA (2002) Plant cell cultures: chemical factories of secondary metabolites. Biotechnol Adv 20:1001–1153.  https://doi.org/10.1016/S0734-9750(02)00007-1 Google Scholar
  168. Ramawat KG, Merillon JM (2008) Bioactive molecules and medicinal plants. Springer, Berlin, pp 1–18CrossRefGoogle Scholar
  169. Ramesha BT, Amna T, Ravikanth G et al (2008) Prospecting for camptothecines from Nothapodytes nimmoniana in the Western Ghats, South India: identification of high-yielding sources of camptothecin and new families of camptothecines. J Chromatogr Sci 46(4):362–368.  https://doi.org/10.1093/chromsci/46.4.362 PubMedCrossRefGoogle Scholar
  170. Ramesha BT, Suma HK, Senthilkumar U et al (2013) New plant sources of the anticancer alkaloid, camptothecin from the Icacinaceae taxa, India. Phytomedicine 20(6):521–527.  https://doi.org/10.1016/j.phymed.2012.12.003 PubMedCrossRefGoogle Scholar
  171. Ramirez-Estrada K, Vidal-Limon H, Hidalgo D et al (2016) Elicitation, an effective strategy for the biotechnological production of the bioactive high-added value compounds in plant cell factories. Molecules 21(2):182.  https://doi.org/10.3390/molecules21020182 PubMedCrossRefGoogle Scholar
  172. Rao SR, Ravishankar GA (2002a) Plant cell cultures: chemical factories of secondary metabolites. Biotechnol Adv 20(2):101–153PubMedCrossRefGoogle Scholar
  173. Rao RS, Ravishankar GA (2002b) Biotransformation of Isoeugenol to vanilla flavor metabolites and capsaicin in freely suspended & immobilized cell cultures of Capsicum frutescens: a study of the influence of b-cyclodextrin and fungal elicitor. Process Biochem 35:341–348CrossRefGoogle Scholar
  174. Ravishankar GA, Rao R (2000) Biotechnological production of phytopharmaceuticals. J Biochem Mol Biol Biophys 4:73–102Google Scholar
  175. Rehman S, Shawl AS, Kour A et al (2008) An endophytic Neurospora sp. from Nothapodytes foetida producing camptothecin. Appl Biochem Microbiol 44(2):203–209CrossRefGoogle Scholar
  176. Reina M, Gonzalez-Coloma A (2007) Structural diversity and defensive properties of diterpenoid alkaloids. Phytochem Rev 6(1):81–95.  https://doi.org/10.1007/s11101-006-9013-5 CrossRefGoogle Scholar
  177. Revadigar V, Shashidhara S, Rajasekharan PE et al (2008) Variability in the chemical constituents in the roots of Coleus forskohlii from different geographical regions of India. Acta Hort 765:245  https://doi.org/10.17660/ActaHortic.2008.765.30 CrossRefGoogle Scholar
  178. Roat C, Ramawat KG (2009) Morphactin and 2iP markedly enhance accumulation of stilbenes in the cell cultures of Cayratia trifolia (L.) Domin. Acta Physiol Plant 31:411–414.  https://doi.org/10.1007/s11738-008-0233-8 CrossRefGoogle Scholar
  179. Rohmer M (1999) The discovery of a mevalonate-independent pathway for isoprenoid biosynthesis in bacteria, algae, and higher plants. Nat Prod Rep 16(5):565–574.  https://doi.org/10.1039/a709175c PubMedCrossRefGoogle Scholar
  180. Rolland F, Moore B, Sheen J (2002) Sugar sensing & signaling in plants. Plant Cell 14:185–205CrossRefGoogle Scholar
  181. Ruan J, Yang M, Fu P, Ye Y, Lin G (2014) Metabolic activation of pyrrolizidine alkaloids: insights into the structural and enzymatic basis. Chem Res Toxicol 27(6):1030–1039PubMedCrossRefGoogle Scholar
  182. Rudrappa T, Neelwarne B, Kumar V et al (2005) Peroxidase production from hairy root cultures of red beet (Beta vulgaris). Electron J Biotechnol 8(2):66–78.  https://doi.org/10.4067/S0717-34582005000200008 CrossRefGoogle Scholar
  183. Ruffoni B, Pistelli L, Bertoli A, Pistelli L (2010) Plant cell cultures: bioreactors for industrial production. In: Giardi MT, Rea G, Berra B (eds) Bio-farms for nutraceuticals, Springer, New York, pp 203–221CrossRefGoogle Scholar
  184. Russowski D, Maurmann N, Rech SB, Fett-Neto AG (2013) Improved production of bioactive valepotriates in whole-plant liquid cultures of Valeriana glechomifolia. Ind Crops Prod 46:253–257.  https://doi.org/10.1016/j.indcrop.2013.01.027 CrossRefGoogle Scholar
  185. Sachin N, Manjunatha BL, Mohana Kumara P et al (2013) Do endophytic fungi possess pathway genes for plant secondary metabolites? Curr Sci 104:178–182Google Scholar
  186. Saito K, Sudo H, Yamazaki M et al (2001) Feasible production of camptothecin by hairy root culture of Ophiorrhriza pumila. Plant Cell Rep 20:267–271.  https://doi.org/10.1007/s002990100320 CrossRefGoogle Scholar
  187. Sankar TYD (2010) In vitro culture of Camptotheca acuminate (Decaisne) in temporary immersion system (TIS): growth, development & production of secondary metabolites. Ph.D. thesis, University Hamburg, GermanyGoogle Scholar
  188. Sato F, Hashimoto T, Hachiya A et al (2001) Metabolic engineering of plant alkaloid biosynthesis. Proc Natl Acad Sci USA 2:367–372.  https://doi.org/10.1073/pnas.98.1.367 CrossRefGoogle Scholar
  189. Sevon N, Oksman-Caldentey KM (2002) Agrobacterium rhizogenes-mediated transformation: root cultures as a source of alkaloids. Planta Med 68(10):859–868.  https://doi.org/10.1055/s-2002-34924 PubMedCrossRefGoogle Scholar
  190. Sharma S, Shrivastava N (2016) Renaissance in phytomedicines: promising implications of NGS technologies. Planta 244(1):19–38.  https://doi.org/10.1007/s00425-016-2492-8 PubMedCrossRefGoogle Scholar
  191. Sharma P, Padh H, Shrivastava N (2013) Hairy root cultures: a suitable biological system for studying secondary metabolic pathways in plants. Eng Life Sci 13(1):62–75.  https://doi.org/10.1002/elsc.201200030 CrossRefGoogle Scholar
  192. Shohael AM, Murthy HN, Hahn EJ, Paek KY (2007a) Methyl jasmonate induced overproduction of eleutherosides in somatic embryos of Eleutherococcus senticosus cultured in bioreactors. Electron J Biotechnol 10(4):633–637.  https://doi.org/10.4067/S0717-34582007000400016 CrossRefGoogle Scholar
  193. Shwab EK, Bok JW, Tribus M, Galehr J, Graessle S, Keller NP (2007) Histone deacetylase activity regulates chemical diversity in Aspergillus. Eukaryot Cell 6(9):1656–1664.  https://doi.org/10.1128/EC.00186-07 PubMedPubMedCentralCrossRefGoogle Scholar
  194. Smetanska I (2008) Production of secondary metabolites using plant cell cultures. In: Stahl U, Donalies UEB, Nevoigt E (eds) Advances in biochemical engineering/biotechnology: food biotechnology, vol 111. Springer, Berlin. pp 187–228.  https://doi.org/10.1007/10_2008_103 Google Scholar
  195. Srivastava S, Srivastava AK (2007) Hairy root culture for mass-production of high-value secondary metabolites. Crit Rev Biotechnol 27(1):29–43.  https://doi.org/10.1080/07388550601173918 PubMedCrossRefGoogle Scholar
  196. Steingroewer J, Bley T, Georgiev V et al (2013) Bioprocessing of differentiated plant in vitro systems. Eng Life Sci 13(1):26–38.  https://doi.org/10.1002/elsc.201100226 CrossRefGoogle Scholar
  197. Stierle A, Strobel G, Stierle D (1993) Taxol & taxane production by Taxomyces andreanae, an endophytic fungus of Pacific yew. Science 260:214–214PubMedCrossRefGoogle Scholar
  198. Su WW, Humphrey AE (1990) Production of rosmarinic acid in high-density perfusion cultures of Anchusa officinalis using a high sugar medium. Biotechnol Lett 12(11):793–798.  https://doi.org/10.1007/BF01022597 CrossRefGoogle Scholar
  199. Su WW, Humphrey AE (2001) Production of plant secondary metabolites from high-density perfusion cultures. In: Furusaki S, Endo I, Matsuno R (eds) Biochemical Engineering for 2001, Springer, Tokyo, pp 266–269Google Scholar
  200. Su WW, Fei L, Su LY (1993) Perfusion strategy for rosmarinic acid production by Anchusa officinalis. Biotechnol Bioeng 42(7):884–890.  https://doi.org/10.1002/bit.260420713 PubMedCrossRefGoogle Scholar
  201. Sudhakar T, Dash SK, Rao RR et al (2013) Do endophytic fungi possess pathway genes for plant secondary metabolites? Curr Sci 104(2):178Google Scholar
  202. Sudo H, Yamakawa T, Yamazaki M, Aimi N, Saito K (2002) Bioreactor production of camptothecin by hairy root cultures of Ophiorrhiza pumila. Biotechnol Lett 24(5):359–363CrossRefGoogle Scholar
  203. Suhas S, Ramesha BT, Ravikanth G et al (2007) Chemical profiling of Nothapodytes nimmoniana populations in the Western Ghats, India for anti-cancer compound, camptothecin. Curr Sci 92(8):1142–1147Google Scholar
  204. Suresh B, Bais HP, Raghavarao KSMS, Ravishankar GA, Ghildyal NP (2005) Comparative evaluation of bioreactor design using Tagetes patula L. hairy roots as a model system. Process Biochem 40(5):1509–1515.  https://doi.org/10.1016/j.procbio.2003.10.017 CrossRefGoogle Scholar
  205. Suryanarayanan TS, Gopalan V, Shaanker RU, Sengupta A, Ravikanth G (2017) Translating endophyte research to applications: prospects and challenges. In: de Azevedo JL, Quecine MC (ed) Diversity and benefits of microorganisms from the tropics, Springer, New York, pp 343–365CrossRefGoogle Scholar
  206. Tabata M, Fujita Y (1985) Production of shikonin by the plant cell cultures. In: Zatlin M, Day P, Hollaender A (eds) Biotechnology in the plant science, Academic Press, Cambridge, pp 207–218CrossRefGoogle Scholar
  207. Tejavathi DH, Rajanna MD, Sowmya R, Gayathramma K (2007) Induction of somatic embryos from cultures of Agave vera-cruz Mill. In Vitro Cell Dev Biol-Plant 43:423–428.  https://doi.org/10.1007/s11627-007-9088-8 CrossRefGoogle Scholar
  208. Thakore D, Srivastava AK, Sinha AK (2013) Yield enhancement strategies for enhancement of indole alkaloids in hairy root cultures of Catharanthus roseus. Intl J Chem Eng Appl 4(3):153.  https://doi.org/10.7763/IJCEA.2013.V4.283 Google Scholar
  209. Thanh NT, Van KN, Paek KY (2007) Effecting of medium composition on biomass and ginsenoside production in cell suspension culture of Panax vietnamensis Haet Grushv. VNUJ Sci Nat Sci Technol 23:269–274Google Scholar
  210. Thomas DR, Penney CA, Majumder A, Walmsley AM (2011) Evolution of plant-made pharmaceuticals. Intl J Mol Sci 12(5):3220–3236.  https://doi.org/10.3390/ijms12053220 CrossRefGoogle Scholar
  211. Tom R, Jardin B, Chavarie C, Rho D, Archambault J (1991) Effect of culture process on alkaloid production by Catharanthus roseus cells: II. Immobilized cultures. J Biotechnol 21(1–2):21–42PubMedCrossRefGoogle Scholar
  212. Trejo-Tapia G, Arias-Castro C, Rodrguez-Mendiola M (2003) Influence of the culture medium constituents & inoculum size on the accumulation of blue pigment & cell growth of Lavandula spica. Plant Cell Tiss Organ Cult 72:7–12.  https://doi.org/10.1023/A:1021270907918 CrossRefGoogle Scholar
  213. Tumova L, Rimakova J, Tuma J, Dusck J (2006) Silybum marianum in vitro-flavolignan production. Plant Cell Environ 52:454–458Google Scholar
  214. Tziampazis E, Sambanis A (1994) Modeling of cell culture processes. Cytotechnol 14(3):191–204CrossRefGoogle Scholar
  215. van der Fits L, Memelink J (2000) ORCA3, a jasmonate-responsive transcriptional regulator of plant primary and secondary metabolism. Science 289:295–297.  https://doi.org/10.1126/science.289.5477.295 PubMedCrossRefGoogle Scholar
  216. Vasanthakumari MM, Jadhav SS, Sachin N et al (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(10):1629–1639.  https://doi.org/10.1007/s11274-015-1916-0 PubMedCrossRefGoogle Scholar
  217. Vasilev N, Schmitz C, Gromping U et al. (2014) Assessment of cultivation factors that affect biomass & geraniol production in the transgenic tobacco cell suspension cultures. PLoS ONE 9(8):e104620.  https://doi.org/10.1371/journal.pone.0104620 PubMedPubMedCentralCrossRefGoogle Scholar
  218. Veerasham C (2004) Medicinal plant biotechnology, CBS, New Delhi, pp 377–419Google Scholar
  219. Venugopalan A, Srivastava S (2015) Enhanced camptothecin production by ethanol addition in the suspension culture of the endophyte, Fusarium solani. Bioresource Technol 188:251–257.  https://doi.org/10.1016/j.biortech.2014.12.106 CrossRefGoogle Scholar
  220. Verpoorte R, Alfermann AW (2000) Metabolic engineering of the plant secondary metabolism, Springer, New York, pp 1–29CrossRefGoogle Scholar
  221. Verpoorte R, Van der Heijden R, Ten Hoopen HJG, Memelink J (1999) Metabolic engineering of plant secondary metabolite pathways for production of fine chemicals. Biotechnol Lett 21(6):467–479.  https://doi.org/10.1023/A:1005502632053 CrossRefGoogle Scholar
  222. Verpoorte R, Contin A, Memelink J (2002) Biotechnology for production of plant secondary metabolites. Phytochem Rev 1(1):13–25.  https://doi.org/10.1023/A:1015871916833 CrossRefGoogle Scholar
  223. Wang G, Qi NM (2009) Perfusion culture of Glycyrrhiza inflata suspension cells in a stir-tank bioreactor. Australian J Bot 57(3):240–246.  https://doi.org/10.1071/BT08187 CrossRefGoogle Scholar
  224. Wang C, Wu J, Mei X (2001) Enhanced taxol production and release in Taxus chinensis cell suspension cultures with selected organic solvents and sucrose feeding. Biotechnol Progr 17(1):89–94.  https://doi.org/10.1021/bp0001359 CrossRefGoogle Scholar
  225. Wang JW, Zheng LP, Wu JY, Tan RX (2006) Involvement of nitric oxide in an oxidative burst, phenylalanine ammonia-lyase activation & taxol production induced by low-energy ultrasound in Taxus yunnanensis cell suspension cultures. Nitric Oxide 15(4):351–358.  https://doi.org/10.1016/j.niox.2006.04.261 PubMedCrossRefGoogle Scholar
  226. Wang GR, Qi NM, Wang ZM (2010a) Application of stir-tank bioreactor for perfusion culture & continuous harvest of Glycyrrhiza inflata suspension cells. Afri J Biotechnol 9(3):347–351.  https://doi.org/10.5897/AJB09.1111 Google Scholar
  227. Wang F, Xu M, Li Q, Sattler I, Lin W (2010b) p-Aminoacetophenonic acids produced by a mangrove endophyte Streptomyces sp.(strain HK10552). Molecules 15(4):2782–2790.  https://doi.org/10.3390/molecules15042782 PubMedCrossRefGoogle Scholar
  228. Wilson SA, Roberts SC (2012) Recent advances towards development and commercialization of plant cell culture processes for the synthesis of biomolecules. Plant Biotechnol J 10(3):249–268.  https://doi.org/10.1111/j.1467-7652.2011.00664.x PubMedCrossRefGoogle Scholar
  229. Wu CH, Murthy HN, Hahn EJ, Paek KY (2008a) Establishment of adventitious root co-culture of Ginseng & Echinacea for the production of secondary metabolites. Acta Physiol Plant 30(6):891–896.  https://doi.org/10.1007/s11738-008-0181-3 CrossRefGoogle Scholar
  230. Wysokinska H, Chmiel A (2006) Produkcja roślinnych metabolitów wtórnych w kulturach organów transformowanych. Biotechnologia 75:124–135Google Scholar
  231. Xu J, Zhang N (2014) On way to commercializing plant cell culture platform for biopharmaceuticals: present status and prospect. Pharma Bioprocess 2(6):499–518CrossRefGoogle Scholar
  232. Xu F, Tao W, Cheng L, Guo L (2006) Strain improvement and optimization of the media of taxol-producing fungus Fusarium maire. Biochem Eng J 31(1):67–73.  https://doi.org/10.1016/j.bej.2006.05.024 CrossRefGoogle Scholar
  233. Yamazaki Y, Sudo H, Yamazaki M et al (2003) Camptothecin biosynthetic genes in hairy roots of Ophiorrhiza pumila: cloning, characterization, & differential expression in tissues and by stress compounds. Plant Cell Physiol 44(4):395–403.  https://doi.org/10.1093/pcp/pcg051 PubMedCrossRefGoogle Scholar
  234. Yamazaki Y, Kitajima M, Arita M et al (2004) Biosynthesis of camptothecin. In silico and in vivo tracer study from [1-13C] glucose. Plant Physiol 134(1):161–170.  https://doi.org/10.1104/pp.103.029389 PubMedPubMedCentralCrossRefGoogle Scholar
  235. Yamazaki M, Mochida K, Asano T et al (2013) Coupling deep transcriptome analysis with untargeted metabolic profiling in Ophiorrhiza pumila to further the understanding of the biosynthesis of the anticancer alkaloid camptothecin and anthraquinones. Plant Cell Physiol 54(5):686–696.  https://doi.org/10.1093/pcp/pct040 PubMedPubMedCentralCrossRefGoogle Scholar
  236. Yang Y, Zhao H, Barrero RA- et al. (2014) Genome sequencing & analysis of paclitaxel-producing endophytic fungus Penicillium aurantiogriseum NRRL62431. BMC Genom 15:69.  https://doi.org/10.1186/1471-2164-15-69 CrossRefGoogle Scholar
  237. Yano A, Takekoshi M (2004) Transgenic plant-derived pharmaceuticals: the practical approach? Expert Opin Biol Ther 4(10):1565–1568PubMedCrossRefGoogle Scholar
  238. Yao J, Weng Y, Dickey A, Wang KY (2015) Plants as factories for human pharmaceuticals: applications and challenges. Intl J Mol Sci 16(12):28549–28565.  https://doi.org/10.3390/ijms161226122 CrossRefGoogle Scholar
  239. Yesil-Celiktas O, Gurel A, Vardar-Sukan F (2010) Large scale cultivation of plant cell and tissue culture in bioreactors. Transworld research network, Trivandrum, Kerala, pp 1–54. http://www.trnres.com/ebook/uploads/celiktas/T_1273559071Celiktas-book.pdf Accessed 4 Sept 2017
  240. Yue W, Ming QL, Lin B et al (2016) Medicinal plant cell suspension cultures: pharmaceutical applications & high-yielding strategies for the desired secondary metabolites. Critical Rev Biotechnol 36(2):215–232.  https://doi.org/10.3109/07388551.2014.923986 CrossRefGoogle Scholar
  241. Zenk MH, El-Shagi H, Arens H et al (1977) Formation of the indole alkaloids serpentine & ajmalicine in the cell suspension cultures of Catharanthus roseus. In: Barz W, Reinhard E, Zenk MH (eds) Plant tissue culture and its biotechnological application. Springer, Berlin, pp 27–43CrossRefGoogle Scholar
  242. Zhang JY, Sun HJ, Song IJ et al (2014) Plant regeneration of Korean wild ginseng (Panax ginseng Meyer) mutant lines induced by γ-irradiation (60 Co) of adventitious roots. J Ginseng Res 38(3):220–225.  https://doi.org/10.1016/j.jgr.2014.04.001 PubMedPubMedCentralCrossRefGoogle Scholar
  243. Zhao J, Davis LC, Verpoorte R (2005) Elicitor signal transduction leading to the production of the plant secondary metabolite. Biotechnol Adv 23:283–333.  https://doi.org/10.1016/j.biotechadv.2005.01.003 PubMedCrossRefGoogle Scholar
  244. Zhong JJ (2001) Biochemical engineering of the production of plant-specific secondary metabolites by cell suspension cultures. In: Scheper T (ed) Advances in the biochemical engineering/biotechnology, vol 72. Springer, Berlin Heidelberg Germany, pp 1–26Google Scholar
  245. Ziv M (2000) Bioreactor technology for plant micropropagation. Hort Rev 24:1–30, ISBN 0-471-33374-3Google Scholar

Copyright information

© Springer Science+Business Media B.V., part of Springer Nature 2017

Authors and Affiliations

  1. 1.Department of Botany, School of Chemical and Life SciencesHamdard UniversityNew DelhiIndia
  2. 2.Plant Tissue Culture LaboratoryNational Biotechnology Development AgencyAbujaNigeria
  3. 3.Indian Institute of Horticultural Research (ICAR)BengaluruIndia

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