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Improving Secondary Metabolite Production in Tissue Cultures

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Abstract

Plant cell and tissue culture has been suggested as an alternative means for year-round production of secondary metabolites with an added potential of increasing yields by culture selection and manipulation, genetic transformation, hairy root cultures, and use of bioreactors for mass production. Secondary metabolite pathways and genes involved in those pathways have been identified, and regulation of transcription and transcription factors has been determined by studying functional genomics in conjunction with data-mining tools of bioinformatics. Besides this, advances in metabolic engineering enable researchers to confer new secondary metabolic pathways to crops by transferring three to five, or more, heterologous genes taken from various other species. As an alternative, the metabolic pathways of useful secondary metabolites have been modified to improve their productivity via genetic transformation. However, there is a need to understand metabolic pathways of secondary metabolism at the molecular level. Plant hairy roots offer a novel and sustainable tissue-based system that preserves multiple specialized cell types believed to be important in maintaining a better consistency in synthesis of bioactive secondary molecules. This paper will review state-of-the-art reports on improving production of secondary metabolites in tissue cultures in various plant species.

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References

  • Allan EJ, Eeswara JP, Jarvis AP, Mordue (Luntz) AJ, Morgan ED, Stuchbury T (2002) Induction of hairy root cultures of Azadirachta indica A. Juss. and their production of azadirachtin and other important insect bioactive metabolites. Plant Cell Rep 21:374–379

    Article  CAS  Google Scholar 

  • Bailey JE (1991) Toward a science of metabolic engineering. Science 252(5013):1668–1675

    Article  CAS  PubMed  Google Scholar 

  • Baque MD, Shiragi MD, Moh SH, Lee EJ, Paek KY (2013) Production of biomass and bioactive compounds by adventitious root suspension cultures of Morinda citrifolia L. in a liquid-phase airlift balloon-type bioreactor. In Vitro Cell Dev Biol Plant 49(6):737–749

    Article  CAS  Google Scholar 

  • Baur J, Sinclair DA (2006) Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov 5:493–506

    Article  CAS  PubMed  Google Scholar 

  • Baur JA, Pearson KJ, Price NL, Jamieson HA et al (2006) Resveratrol improves health and survival of mice on a high-calorie diet. Nature 444:37–342

    Article  Google Scholar 

  • Bender L, Kumar A (2001) From soil to cell: a broad approach to plant life. Giessen Electron. Library GEB, pp 1–5. http://geb.uni-giessen.de/geb/volltexte/2006/3039/pdf/Festschrift Neumann-2001.pdf

  • Bhadra R, Morgan JA, Shanks JV (1998) Transient studies of light- adapted cultures of hairy roots of Catharanthus roseus: growth and indole alkaloid accumulation. Biotech Bioeng 60:670–678

    Article  CAS  Google Scholar 

  • Bopana N, Saxena S (2010) Biotechnological aspects of secondary metabolite production pp 451–473. In: Kumar A, Sopory S (eds) Applications of plant biotechnology: in vitro propagation, plant transformation and secondary metabolite production. I.K. International, New Delhi, p 606

    Google Scholar 

  • Cardillo AB, Giulietti AM, Palazón J, Bonfill M (2013) Influence of hairy root ecotypes on production of tropane alkaloids in Brugmansia candida. Plant Cell Tissue Organ Cult 114(3):305–312

    Article  CAS  Google Scholar 

  • Dehghan E, Hakkinen ST, Oksman-Caldentey KM, Ahmadi FS (2012) Production of tropane alkaloids in diploid and tetraploid plants and in vitro hairy root cultures of Egyptian henbane (Hyoscyamus muticus L.). Plant Cell Tissue Organ Cult 110:35–44

    Article  CAS  Google Scholar 

  • Delmas D, Lancon A, Colin D, Jannin B, Latruffe N (2006) Resveratrol as a chemopreventive agent: a promising molecule for fighting cancer. Curr Drug Targets 7:423–442

    Article  CAS  PubMed  Google Scholar 

  • Dewey RE, Xie J (2013) Molecular genetics of alkaloid biosynthesis in Nicotiana tabacum. Phytochemistry 94:10–27

    Article  CAS  PubMed  Google Scholar 

  • Donnez D, Kim K-H, Antoine S, Conreux A, De Luca V, Jeandet P, Clement C, Courot E (2011) Bioproduction of resveratrol and viniferins by an elicited grapevine cell culture in a 2 L stirred bioreactor. Process Biochem 46:1056–1062

    Article  CAS  Google Scholar 

  • Dumontet C, Jordan MJ (2010) Microtubule-binding agents: a dynamic field of cancer therapeutics. Nat Rev 9:790–803

    CAS  Google Scholar 

  • Farrow SC, Hagel JM, Facchini PJ (2012) Transcript and metabolite profiling in cell cultures of 18 plant species that produce benzylisoquinoline alkaloids. Phytochemistry 77:79–88

    Article  CAS  PubMed  Google Scholar 

  • Favretto D, Piovan A, Filippini R, Caniato R (2001) Monitoring the production yields of vincristine and vinblastine in Catharanthus roseus from somatic embryogenesis. Semi-quantitative determination by flow-injection electrospray ionization mass spectrometry. Rapid Commun Mass Spectrom 15:364–369

    Article  CAS  PubMed  Google Scholar 

  • Federici E, Touché A, Choquart S, Avanti O, Fay L, Offord E, Courtois D (2003) High isoflavone content and estrogenic activity of 25 year-old Glycine max tissue cultures. Phytochemistry 64:717–724

    Article  CAS  PubMed  Google Scholar 

  • Fernandez H, Kumar A, Revilla BMA (2010) Working with ferns: issues and applications. Springer, Dresden, Germany, p 350

    Google Scholar 

  • Flores HE (1992) Plant roots as chemical factories. Chem Ind 10:374–377

    Google Scholar 

  • Frankel E, Waterhouse A, Kinsella J (1993) Inhibition of human LDL oxidation by resveratrol. Lancet 341:1103–1104

    Article  CAS  PubMed  Google Scholar 

  • Gao R, Wu S-Q, Piao X-C, Park S-Y, Lian M-L (2014) Micropropagation of Cymbidium sinense using continuous and temporary airlift bioreactor systems. Acta Physiol Plant 36:117–124

    Article  CAS  Google Scholar 

  • Goyal S, Ramawat KG (2008a) Ethrel treatment enhanced isoflavonoids accumulation in cell suspension cultures of Pueraria tuberosa, a woody legume. Acta Physiol Plant 30:849–853

    Article  CAS  Google Scholar 

  • Goyal S, Ramawat KG (2008b) Synergistic effect of morphactin on cytokinin-induced production of isoflavonoids in cell cultures of Pueraria tuberosa (Roxb. Ex. Willd.) DC. Plant Growth Regul 55:175–181

    Article  CAS  Google Scholar 

  • Han J-Y, Wang H-Y, Choi Y-E (2013) Production of dammarenediol-II triterpene in a cell suspension culture of transgenic tobacco. Plant Cell Rep 33(2):225–233

    Article  CAS  PubMed  Google Scholar 

  • He X-Z, Blount JW, Ge S, Tang Y, Dixon RA (2011) A genomic approach to isoflavone biosynthesis in kudzu (Pueraria lobata). Planta 233:843–855

    Article  CAS  PubMed  Google Scholar 

  • Huang TK, McDonald KA (2012) Bioreactor systems for in vitro production of foreign proteins using plant cell cultures. Biotechnol Adv 30:398–409

    Article  CAS  PubMed  Google Scholar 

  • Jouanin L (1984) Restriction map of an agropine-type Ri plasmid and its homologies with Ti plasmids. Plasmid 12:91–102

    Article  CAS  PubMed  Google Scholar 

  • Kim EK, Hahn EJ, Murthy HN, Paek KY (2004) Enhanced shoot and bulblet proliferation of garlic (Album sativum L.) in bioreactor systems. J Hortic Sci Biotechnol 79:818–822

    Google Scholar 

  • Kochkin DV, Kachala VV, Shashkov AS, Chizhov AO, Chirva VY, Nosov AM (2013) Malonyl-ginsenoside content of a cell-suspension culture of Panax japonicus var. repens. Phytochemistry 93:18–26

    Article  CAS  PubMed  Google Scholar 

  • Kokotkiewicz A, Luczkiewicz M, Kowalski W, Badura A, Piekus N, Bucinski A (2013) Isoflavone production in Cyclopia subternata Vogel (honeybush) suspension cultures grown in shake flasks and stirred-tank bioreactor. Appl Microbiol Biotechnol 97(19):8467–8477

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kong L, von Aderkas P (2007) Genotype effects on ABA consumption and somatic embryo maturation in interior spruce (Picea glauca 9 engelmanni). J Exp Bot 58:1525–1531

    Article  CAS  PubMed  Google Scholar 

  • Kong W, Wei J, Abidi P, Lin M, Inaba S, Li C, Wang Y, Wang Z, Si S, Pan H, Wang S, Wu J, Wang Y, Li Z, Liu J, Jiang JD (2004) Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins. Nat Med 10:1344–1351

    Article  CAS  PubMed  Google Scholar 

  • Kong L, Holtz CT, Nairn CJ, Houke H, Powell WA, Baier K, Merkle SA (2013) Application of airlift bioreactors to accelerate genetic transformation in American chestnut. Plant Cell Tissue Organ Cult 117(1):39–50

    Article  Google Scholar 

  • Kong L, Holtz CT, Nairn CJ, Houke H, Powell WA, Baier K, Merkle SA (2014) Application of airlift bioreactors to accelerate genetic transformation in American chestnut. Plant Cell Tissue Organ Cult 117:39–50

    Article  CAS  Google Scholar 

  • Kumar A (2010) Plant genetic transformation and molecular markers. Pointer Publishers, Jaipur, p 288

    Google Scholar 

  • Kumar A (2014) ACCESS Improvement of Fenugreek through Breeding Approaches and In Vitro Applications. In: Basu SK Agoramoorthy G (eds) American Journal of social issues and humanities. pp 120–127

    Google Scholar 

  • Kumar A, Roy S (2006) Plant biotechnology and its applications in tissue culture. I.K. International, Delhi, p 307

    Google Scholar 

  • Kumar A, Roy S (2011) Plant tissue culture and applied plant biotechnology. Avishkar Publishers, Jaipur, p 346

    Google Scholar 

  • Kumar A, Shekhawat NS (2009) Plant tissue culture and molecular markers: their role in improving crop productivity. I.K. International, New Delhi, p 688

    Google Scholar 

  • Kumar A, Sopory S (2008) Recent advances in plant biotechnology and its applications. I.K. International, New Delhi, p 718

    Google Scholar 

  • Kumar A, Sopory S (2010) Applications of plant biotechnology: in vitro propagation, plant transformation and secondary metabolite production. I.K. International, New Delhi, p 606

    Google Scholar 

  • Kumar A, Sharma M, Basu SK, Asif M, Li XP, Chen X (2014) Plant molecular breeding: perspectives from the plant biotechnology and market assisted selection. In: Benkeblia N (ed) Omics technologies and crops improvement. CRC Press, Boca Raton, pp 153–168

    Google Scholar 

  • Lee OR, Yang DC, Chung HJ, Min BH (2011) Efficient in vitro plant regeneration from hybrid rhizomes of Cymbidium sinense seeds. Hortic Environ Biotechnol 52:303–308

    Article  Google Scholar 

  • Lindsey K, Yeoman MM (1983) The relationship between growth rate, differentiation and alkaloid accumulation in cell cultures. J Exp Bot 34:1055–1065

    Article  CAS  Google Scholar 

  • Lorence A, Nessler CL (2004) Camptothecin, over four decades of surprising findings. Phytochemistry 65:2735–2749

    Article  CAS  PubMed  Google Scholar 

  • Magnotta M, Murata J, Chen J, De Luca V (2007) Expression of deacetylvindoline-4-O-acetyltransferase in Catharanthus roseus hairy roots. Phytochemistry 68:1922–1931

    Article  CAS  PubMed  Google Scholar 

  • Maldonado-Mendoza IE, Ayora-Talavera T, Loyola-Vargas VM (1993) Establishment of hairy root cultures of Datura stramonium. Characterization and stability of tropane alkaloid production during long periods of subculturing. Plant Cell Tiss Org Cult 33:321–329

    Article  CAS  Google Scholar 

  • Mallol A, Cusido RM, Palazon J, Bonfill M, Morales C, Pinol MT (2001) Ginsenoside production in different phenotypes of Panax ginseng transformed roots. Phytochemistry 57(3):365–371

    Article  CAS  PubMed  Google Scholar 

  • Mathur A, Shukla YN, Pal M, Ahuja PS, Uniyal GC (1994) Saponin production in callus and cell suspension cultures of Panax quinquefolium. Phytochemistry 35:1221–1225

    Article  CAS  Google Scholar 

  • Murthy HN, Lee E-J, Paek K-Y (2014) Production of secondary metabolites from cell and organ cultures: strategies and approaches for biomass improvement and metabolite accumulation. Plant Cell Tiss Org Cult (PCTOC) 118(1):1–16

    Article  CAS  Google Scholar 

  • Nakagawa A, Minami H, Kim J-S, Koyanagi T, Katayama T, Sato F, Kumagai H (2011) A bacterial platform for fermentative production of plant alkaloids. Nat Commun 2:326

    Article  PubMed Central  PubMed  Google Scholar 

  • Neumann K, Kumar A, Imani J (2009) Plant cell and tissue culture – a tool in biotechnology basics and application. Springer, Berlin/Heidelberg, Germany, p 333

    Google Scholar 

  • Pasquali G, Porto DD, Fett-Netto AG (2006) Metabolic engineering of cell cultures versus whole plant complexity in production of bioactive monoterpene indole alkaloids: recent progress related to old dilemma. J Biosci Bioeng 101(4):287–296

    Article  CAS  PubMed  Google Scholar 

  • Palazon J, Cusido’ RM, Gonzalo J, Bonfill M, Morales C, Pinol MT (1998) Relation between the amount of rolC gene product and indole alkaloid accumulation in Catharanthus transformed root cultures. J Plant Physiol 153:712–718

    Article  CAS  Google Scholar 

  • Patisaul HB, Jefferson W (2010) The pros and cons of phytoestrogens. Front Neuroendocrinol 31:400–419

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Rahman L, Kouno H, Hashiguchi Y, Yamamoto H, Narbad A, Parr A, Walton N, Ikenaga T, Kitamura Y (2009) HCHL expression in hairy roots of Beta vulgaris yields a high accumulation of p-hydroxybenzoic acid (pHBA) glucose ester, and linkage of pHBA into cell walls. Bioresour Technol 100:4836–4842

    Article  CAS  PubMed  Google Scholar 

  • Ramawat KG, Rideau M, Chenieux J-C (1985) Growth and quaternary alkaloid production in differentiating and nondifferentiating strains of Ruta graveolens. Phytochemistry 24:441–445

    Article  CAS  Google Scholar 

  • Roupe K, Remsberg C, Yanez J, Davies N (2006) Pharmacometrics of stilbenes: seguing towards the clinic. Curr Clin Pharmacol 1:81–101

    Article  CAS  PubMed  Google Scholar 

  • Saito K, Sudo H, Yamazaki M, Koseki-Nakamura M, Kitajima M, Takayama H, Aimi N (2001) Feasible production of camptothecin by hairy root culture of Ophiorrhiza pumila. Plant Cell Rep 20:267–271

    Article  CAS  Google Scholar 

  • Shadwick FS, Doran PM (2007) Propagation of plant viruses in hairy root cultures: a potential method for in vitro production of epitope vaccines and foreign proteins. Biotechnol Bioeng 96:570–583

    Article  CAS  PubMed  Google Scholar 

  • Sharma M, Sharma A, Kumar A, Basu SK (2011) Enhancement of secondary metabolites in cultured plant cells through stress stimulus. Am J Plant Physiol 6:50–71

    Article  CAS  Google Scholar 

  • Sharma V, Goyal S, Ramawat KG (2009) Scale up production of isoflavonoids in cell suspension cultures of Pueraria tuberosa grown in shake flasks and bioreactor. Eng Life Sci 9:267–271

    Article  CAS  Google Scholar 

  • Shinde AN, Malpathak N, Fulzele DP (2009a) Studied enhancement strategies for phytoestrogens production in shake flasks by suspension culture of Psoralea corylifolia. Bioresour Technol 100:1833–1839

    Article  CAS  PubMed  Google Scholar 

  • Shinde AN, Malpathak N, Fulzele DP (2009b) Optimized production of isoflavones in cell cultures of Psoralea corylifolia L. using elicitation and precursor feeding. Biotechnol Bioproc Eng 14:612–618

    Article  CAS  Google Scholar 

  • Sirikantaramas S, Sudo H, Asano T, Yamazaki M, Saito K (2007) Transport of camptothecin in hairy roots of Ophiorrhiza pumila. Phytochemistry 68(22–24):2881–2886

    Article  CAS  PubMed  Google Scholar 

  • Sivakumar G, Yu K, Lee J, Kang J, Lee L, Kim W, Paek K (2006) Tissue cultured mountain ginseng adventitious roots. Eng Life Sci 6:372–383

    Article  CAS  Google Scholar 

  • Srivastava S, Srivastava AK (2013) Production of the biopesticide azadirachtin by hairy root cultivation of Azadirachta indica in liquid-phase bioreactors. Appl Biochem Biotechnol 171(6):1351–1361

    Article  CAS  PubMed  Google Scholar 

  • Tabata M, Yamamoto H, Hiraoka N, Konoshima M (1972) Organization and alkaloid production in tissue cultures of Scopolia parviflora. Phytochemistry 11:949–955

    Article  CAS  Google Scholar 

  • Tanaka O, Kasai R (1984) Saponins of ginseng and related plants. In: Herz W, Grisebach H, Kirby GW, Tamm CH (eds) Progress in the chemistry of organic natural products. Springer, Berlin, pp 1–76

    Google Scholar 

  • Terrier B, Courtois D, Hénault N, Cuvier A, Bastin M, Aknin A, Dubreuil J, Pétiard V (2007) Two new disposable bioreactors for plant cell culture: the wave and undertow bioreactor and the slug bubble bioreactor. Biotechnol Bioeng 96:914–923

    Article  CAS  PubMed  Google Scholar 

  • Thwe AA, Mai NTT, Li X, Kim Y, Kim YB, Uddin MR, Kim YS, Bae H, Kim HH, Lee MY, Park SU (2012) Production of astragaloside and flavones from adventitious root cultures of Astragalus membranaceus var. mongholicus. Plant Omics J 5:466–470

    CAS  Google Scholar 

  • Verpoorte R (2000) Secondary metabolism. In: Verpoorte R, Alfermann AW (eds) Metabolic engineering of plant secondary metabolism. Kluwer, Dordrecht, pp 1–29

    Chapter  Google Scholar 

  • Wallace J (1998) Finding the products and companies you can trust. Appendix: NC 5 selecting High quality dietary supplements. Haw- thorn Health & Nutrition Institute

    Google Scholar 

  • Wang C-T, Liu H, Gao X-S, Zhang H-X (2010) Overexpression of G10H and ORCA3 in the hairy roots of Catharanthus roseus improves catharanthine production. Plant Cell Rep 29(8):887–894

    Article  CAS  PubMed  Google Scholar 

  • Washida D, Shimomura K, Nakajima Y, Takido M, Kitanaka S (1998) Ginsenosides in hairy roots of a Panax hybrid. Phytochemistry 49:2331–2335

    Article  CAS  Google Scholar 

  • Watts KT, Lee PC, Schmidt-Dannert C (2006) Biosynthesis of plant- specific stilbene polyketides in metabolically engineered Escherichia coli. BMC Biotechnol 6:22

    Article  PubMed Central  PubMed  Google Scholar 

  • Wu Q, Wang M, Simon JE (2003) Determination of isoflavones in red clover and related species by high-performance liquid chromatography combined with ultraviolet and mass spectrometric detection. J Chromatogr A 1016:195–209

    Article  CAS  PubMed  Google Scholar 

  • Wu T, Bligh SWA, Wang Z-T, Gu L-H et al (2005) Simultaneous determination of six isoflavonoids in commercial Radix astragali by HPLC-UV. Fitoterapia 76:157–165

    Article  CAS  PubMed  Google Scholar 

  • Wu SQ, Lian ML, Gao R, Park SY, Piao XC (2011) Bioreactor application on adventitious root culture of Astragalus membranaceus. In Vitro Cell Dev Biol Plant 47:719–724

    Article  CAS  Google Scholar 

  • Wu S-Q, Yu X-K, Lian M-L, Park S-Y, Piao X-C (2014) Several factors affecting hypericin production of Hypericum perforatum during adventitious root culture in airlift bioreactors. Acta Physiol Plant 36(4):975–981

    Article  CAS  Google Scholar 

  • Yang JF, Piao XC, Sun D, Lian ML (2010) Production of protocorm- like bodies with bioreactor and regeneration in vitro of Oncidium ‘Sugar Sweet’. Sci Hortic 125:712–717

    Article  CAS  Google Scholar 

  • Yoshikawa T, Furuya T (1987) Saponin production by cultures of Panax ginseng transformed with Agrobacterium rhizogenes. Plant Cell Rep 6:449–453

    CAS  PubMed  Google Scholar 

  • Yu KW, Gao WY, Hahn EJ, Paek KY (2002) Jasmonic acid improves ginsenoside accumulation in adventitious root culture of Panax ginseng C.A. Meyer. Biochem Eng J 11:211–215

    Article  CAS  Google Scholar 

  • Zhang L, Ding R, Chai Y, Bonfill M, Moyano E, Oksman-Caldentey KM, Xu T, Pi Y, Wang Z, Zhang H, Kai G, Liao Z, Sun X, Tang K (2004) Engineering tropane biosynthetic pathway in Hyoscyamus niger hairy root cultures. Proc Natl Acad Sci U S A 101:6786–6791

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zhao Y, Sun W, Wang Y, Saxena PK, Liu CZ (2012a) Improved mass multiplication of Rhodiola crenulata shoots using temporary immersion bioreactor with forced ventilation. Appl Biochem Biotechnol 166:1480–1490

    Article  CAS  PubMed  Google Scholar 

  • Zhao B, Foster A, Agblevor A, Ritesh KC, Jelesko GJ (2012b) Enhanced production of the alkaloid nicotine in hairy root cultures of Nicotiana tabacum L. Plant Cell Tiss Org Cult 113(1):121–129

    Article  Google Scholar 

  • Zhou M-L, Zhu X-M, Shao J-R, Tang Y-X, Wu Y-M (2011) Production and metabolic engineering of bioactive substances in plant hairy root culture. Appl Microbiol Biotechnol 90:1229–1239

    Article  CAS  PubMed  Google Scholar 

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Kumar, A. (2015). Improving Secondary Metabolite Production in Tissue Cultures. In: Bahadur, B., Venkat Rajam, M., Sahijram, L., Krishnamurthy, K. (eds) Plant Biology and Biotechnology. Springer, New Delhi. https://doi.org/10.1007/978-81-322-2283-5_20

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