Skip to main content

Hairy Root Cultures for Monoterpene Indole Alkaloid Pathway: Investigation and Biotechnological Production

  • Chapter
  • First Online:
Book cover Hairy Roots

Abstract

Terpene indole alkaloids (TIAs) comprise a major group of alkaloids as more than 3000 TIAs are known with resilient and beneficial biological activities. These TIAs exhibit varied structural intricacy with a characteristically common tryptophan or tryptamine residue with a carbon tail of terpenoid origin derived from the dimethylallyl pyrophosphate (DMAPP) and isopentenyl pyrophosphate (IPP) pathways. According to the number of isoprene units, monoterpene indole alkaloids (MIAs) comprise the major class of TIAs that have two isoprene units originated from secologanin. MIAs have been extensively investigated for their immense pharmaceutical importance as these compounds possess strong properties against various types of cancers, diseases of the central nervous systems, malaria, hypertension, and major cardiac ailments. Keeping in mind their immense pharmaceutical worth and ever-increasing demand from the pharmaceutical world, solicitous attention is needed on their biological production and scientific strategies to abate the demand and supply ratio. Furthermore, a holistic understanding is always required to explore intimately interconnected facts of synthesis and regulation of these metabolites. In this context, with their reasonable competence, the hairy root cultures (HRCs) have gained center-stage focus as an excellent in vitro system for different scientific investigatory objectives. This chapter provides condensed information about various MIAs, their biosynthesis in native plants, and contribution of HRCs to investigate the operational and regulatory mechanism of their in vitro and in planta biosynthesis.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Akhgari A, Laakso I, Seppänen-Laakso T, Yrjönen T, Vuorela H, Oksman-Caldentey KM, Rischer H (2015a) Determination of terpenoid indole alkaloids in hairy roots of Rhazya stricta (Apocynaceae) by GC-MS. Phytochem Anal 26(5):331–338

    Article  CAS  PubMed  Google Scholar 

  • Akhgari A, Yrjönen T, Laakso I, Vuorela H, Oksman-Caldentey KM, Rischer H (2015b) Establishment of transgenic Rhazya stricta hairy roots to modulate terpenoid indole alkaloid production. Plant Cell Rep 34(11):1939–1952

    Article  CAS  PubMed  Google Scholar 

  • Arora R, Malhotra P, Mathur AK, Mathur A, Govil CM, Ahuja PS (2010) Anticancer alkaloids of Catharanthus roseus: transition from traditional to modern medicine. Herbal medicine: a cancer chemopreventive and therapeutic perspective. Jaypee Brothers Medical Publishers Pvt. Ltd, New Delhi, pp 292–310

    Google Scholar 

  • Asano T, Kobayashi K, Kashihara E, Sudo H, Sasaki R, Iijima Y, Aoki K, Shibata D, Saito K, Yamazaki M (2013) Suppression of camptothecin biosynthetic genes results in metabolic modification of secondary products in hairy roots of Ophiorrhiza pumila. Phytochemistry 91:128–139

    Article  CAS  PubMed  Google Scholar 

  • Aslam J, Khan SH, Siddiqui ZH, Fatima Z, Mehpara M et al (2010) Catharanthus roseus (L.) G. Don. An important drug: it’s applications and production. Pharmacie Globale (IJCP) 4(12):1–16

    Google Scholar 

  • Ayora T, Joseph C, Edmundo LG, Víctor LV (2002) Overexpression in Catharanthus roseus hairy roots of a truncated hamster 3-Hydroxy-3-Methylglutaryl-CoA reductase gene. App Biochem Biotechnol 97:135–145

    Article  Google Scholar 

  • Barleben L, Panjikar S, Ruppert M, Koepke J, Stöckigt J (2007) Molecular architecture of Strictosidine glucosidase: the gateway to the biosynthesis of the Monoterpenoid indole alkaloid family. Plant Cell 19:2886–2897

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Benayad S, Ahamada K, Lewin G, Evanno L, Poupon E (2016) Preakuammicine: a long-awaited missing link in the biosynthesis of monoterpene indole alkaloids. Eur J Org Chem 2016:1494–1499

    Article  CAS  Google Scholar 

  • Benjamin BD, Roja G, Heble MR (1993) Agrobacterium rhizogenes mediated transformation of Rauvolfia serpentina: regeneration and alkaloid synthesis. Plant Cell Tissue Organ Cult 35:253–257

    Article  CAS  Google Scholar 

  • Benyammi R, Paris C, Khelifi-Slaoui M, Zaoui D, Belabbassi O, Bakiri N, Meriem Aci M, Harfi B, Malik S, Makhzoum A, Desobry S, Khelifi L (2016) Screening and kinetic studies of catharanthine and ajmalicine accumulation and their correlation with growth biomass in Catharanthus roseus hairy roots. Pharm Biol 54(10):2033–2043

    Article  CAS  PubMed  Google Scholar 

  • Bhadra R, Shanks JV (1997) Transient studies of nutrient uptake, growth and indole alkaloid accumulation in heterotrophic cultures of hairy roots of Catharanthus roseus. Biotechnol Bioeng 55:527–534

    Article  CAS  PubMed  Google Scholar 

  • Bhadra R, Vani S, Shanks JV (1993) Production of indole alkaloids by selected hairy root lines of Catharanthus roseus. Biotechnol Bioeng 41(5):581–592

    Article  CAS  PubMed  Google Scholar 

  • Binder BY, Peebles CA, Shanks JV, San KY (2009) The effects of UV-B stress on the production of terpenoid indole alkaloids in Catharanthus roseus hairy roots. Biotechnol Prog 25:861–865

    Article  CAS  PubMed  Google Scholar 

  • Buckingham J, Baggaley K, Roberts A, Szabo L (eds) (2010) Dictionary of alkaloids. CRC Press Taylor & Francis Group, Boca Raton

    Google Scholar 

  • Chang SH, Chen FH, Tsay JY, Chen J, Huang CY, Lu WL, HO CK (2014) Establishment of hairy root cultures of Nothapodytes nimmoniana to produce camptothecin. Taiwan J For Sci 29(3):193–204

    Google Scholar 

  • Costa MMR, Hilliou F, Duarte P, Pereira LG, Almeida I, Leech M, Memelink J, Barcelo AR, Sottomayor M (2008) Molecular cloning and characterization of a vacuolar class III peroxidase involved in the metabolism of anticancer alkaloids in Catharanthus roseus. Plant Physiol 146:403–417

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cui L, Ni X, Ji Q, Teng X, Yang Y, Wu C, Zekria D, Zhang D, Kai G (2015) Co-overexpression of geraniol-10-hydroxylase and strictosidine synthase improves anti-cancer drug camptothecin accumulation in Ophiorrhiza pumila. Sci Rep 5:8227

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • De Luca V, Marineau C, Brission N (1989) Molecular cloning and analysis of cDNA encoding a plant tryptophan decarboxylase: comparison with animal dopa decarboxylases. Proc Natl Acad Sci USA 86:2582–2586

    Article  PubMed  PubMed Central  Google Scholar 

  • De Luca V, Salim V, Levac D, Atsumi SM, Yu F (2012) Discovery and functional analysis of monoterpenoid indole alkaloid pathways in plants. Methods Enzymol 515:207–229

    Article  PubMed  CAS  Google Scholar 

  • Falkenhagen H, Stockigt J, Kuzovkina IN, Alterman IE, Kolshorn H (1993) Indole alkaloids from the hairy roots of Rauvolfia serpentina. Can J Chem 71:2201–2203

    Article  CAS  Google Scholar 

  • Ferreres F, Figueiredo R, Bettencourt S, Carqueijeiro I, Oliveira J et al (2011) Identification of phenolic compounds in isolated vacuoles of the medicinal plant Catharanthus roseus and their interaction with vacuolar class III peroxidase: an H2O2 affair? J Exp Bot 62:2841–2854

    Article  CAS  PubMed  Google Scholar 

  • Geerlings A, Hallard D, Caballero AM, Cardso IL, Heijden rV, Verpoorte R (1999) Alkaloid production by a Cinchona officinalis ‘Ledgeriana’ hairy root culture containing constitutive expression constructs of tryptophan decarboxylase and strictosidine synthase cDNAs from Catharanthus roseus. Plant Cell Rep 19(2):191–196

    Article  CAS  PubMed  Google Scholar 

  • Geerlings A, Memelink J, van der Heijden R, Verpoorte R (2000) Molecular cloning and analysis of strictosidine β-D-glucosidase, an enzyme in terpenoid indole alkaloid biosynthesis in Catharanthus roseus. J Biol Chem 275:3051–3056

    Article  CAS  PubMed  Google Scholar 

  • Gerasimenko I, Sheludko Y, Maand X, Stockigt J (2002) Heterologous expression of a Rauvolfia cDNA encoding strictosidine glucosidase, a biosynthetic key to over 2000 monoterpenoid indole alkaloids. Eur J Biochem 269:2204–2213

    Article  CAS  PubMed  Google Scholar 

  • Glenn WS, Nims E, O’Connor SE (2011) Reengineering a tryptophan halogenase to preferentially chlorinate a direct alkaloid precursor. J Am Chem Soc 133:19346–19349

    Article  CAS  PubMed  Google Scholar 

  • Goddijn OJ, Lohman FP, de Kam RJ, Schilperoort RA, Hoge JH (1994) Nucleotide sequence of the tryptophan decarboxylase gene of Catharanthus roseus and expression of tdc-gus a gene fusions in Nicotiana tabacum. Mol Gen Genet 242(2):217–225

    Article  CAS  PubMed  Google Scholar 

  • Goddijn OJ, Pennings EJ, van der Helm P, Schilperoort RA, Verpoorte R, Hoge JH (1995) Overexpression of a tryptophan decarboxylase cDNA in Catharanthus roseus crown gall calluses results in increased tryptamine levels but not in increased terpenoid indole alkaloid production. Transgenic Res 4(5):315–323

    Article  CAS  PubMed  Google Scholar 

  • Goklany S, Loring RH, Glick J, Lee-Parsons CW (2009) Assessing the limitations to terpenoid indole alkaloid biosynthesis in Catharanthus roseus hairy root cultures through gene expression profiling and precursor feeding. Biotechnol Prog 25(5):1289–1296

    Article  PubMed  CAS  Google Scholar 

  • Goklany S, Rizvi NF, Loring RH, Cram EJ, Lee-Parsons CW (2013) Jasmonate-dependent alkaloid biosynthesis in Catharanthus roseushairy root cultures is correlated with the relative expression of Orca and Zct transcription factors. Biotechnol Prog 29(6):1367–1376

    Article  CAS  PubMed  Google Scholar 

  • Guillon S, Gantet P, Thiersault M, Rideau M, Trémouillaux-Guiller J (2008) Hairy roots of Catharanthus roseus: efficient routes to monomeric indole alkaloid production. In: Ramawat KG, Merillon JM (eds) Bioactive molecules and medicinal plants. Springer, Heidelberg, Berlin, pp 285–295

    Chapter  Google Scholar 

  • Gurung P, De P (2017) Spectrum of biological properties of Cinchona alkaloids: a brief review. J Pharmacogn Phytochem 6(4):162–166

    Google Scholar 

  • Hong S-B, Peebles CA, Shanks JV, San K-Y, Gibson SI (2006) Expression of the Arabidopsis feedback-insensitive anthranilate synthase holoenzyme and tryptophan decarboxylase genes in Catharanthus roseus hairy roots. J Biotechnol 122:28–38

    Article  CAS  PubMed  Google Scholar 

  • Hughes EH, Hong SB, Gibson SI, Shanks JV, San KY (2004a) Expression of a feedback-resistant anthranilate synthase in Catharanthus roseus hairy roots provides evidence for tight regulation of terpenoid indole alkaloid levels. Biotechnol Bioeng 86:718–727

    Article  CAS  PubMed  Google Scholar 

  • Hughes EH, Hong S-B, Gibson SI, Shanks JV, San KY (2004b) Metabolic engineering of the indole pathway in Catharanthus roseus hairy roots and increased accumulation of tryptamine and serpentine. Metab Eng 6:268–276

    Article  CAS  PubMed  Google Scholar 

  • Isah T, Mujib A (2015) Camptothecin from Nothapodytes nimmoniana: review on biotechnology applications. Acta Physiol Plant 37(6):106

    Article  CAS  Google Scholar 

  • Islas I, Loyola-Vargas VM, de Lourdes M-HM (1994) Tryptophan decarboxylase activity in transformed roots from Catharanthus roseus and its relationship to tryptamine, ajmalicine, and catharanthine accumulation during the culture cycle. In Vitro Cell Dev Biol Plant 30:81–83

    Article  Google Scholar 

  • Islas-Flores I, Moreno-Valenzuela O, Minero-García Y, Loyola-Vargas VM, Miranda-Ham Mde L (2002) Tryptophan decarboxylase from transformed roots of Catharanthus roseus. Mol Biotechnol 21(3):211–216

    Article  CAS  PubMed  Google Scholar 

  • Kacprzak KM (2013) Chemistry and biology of cinchona alkaloids. In: Ramawat KG, MÕrillon JM (eds) Natural products. Springer, Berlin, pp 605–641

    Chapter  Google Scholar 

  • Kala CP, Dhyani PP, Sajwan BS (2006) Developing the medicinal plants sector in northern India: challenges and opportunities. J Ethnobiol Ethnomed 2:32–47

    Article  PubMed Central  Google Scholar 

  • Kamble S, Roja G, Eapen S (2011) Production of camptothecin by hairy roots and regenerated transformed shoots of Ophiorrhiza rugosa var. decumbens. Nat Prod Res 25(18):1762–1765

    Article  CAS  PubMed  Google Scholar 

  • Kedari P, Malpathak N (2013) Hairy root cultures of Chenomorpha fragrans (moon) Alston: a potential plant for camptothecin production. Indian J Biotechnol 13:231–235

    Google Scholar 

  • Khazir J, AhmadMir B, Pilcher L, Darren LR (2014) Role of plants in anticancer drug discovery. Phytochem Lett 7:173–181

    Article  CAS  Google Scholar 

  • Kitajima M, Yoshida S, Yamagata K, Nakamura M, Takayama H, Saito K, Seki H, Aimi N (2002) Camptothecin-related alkaloids from hairy roots of Ophiorrhiza pumila. Tetrahedron 58(45):9169–9178

    Article  CAS  Google Scholar 

  • Leduc M, Tikhomiroff C, Cloutier M, Perrier M, Jolicoeur M (2006) Development of a kinetic metabolic model: application to Catharanthus roseus hairy root. Bioprocess Biosyst Eng 28(5):295–313

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Levac D, Murata J, Kim WS, De Luca V (2008) Application of carborundum abrasion for investigating leaf epidermis: molecular cloning of Catharanthus roseus 16-hydroxy-tabersonine-16-Omethyltransferase. Plant J 53:225–236

    Article  CAS  PubMed  Google Scholar 

  • Li M, Peebles CA, Shanks JV, San KY (2011) Effect of sodium nitroprusside on growth and terpenoid indole alkaloid production in Catharanthus roseus hairy root cultures. Biotechnol Prog 27(3):625–630

    Article  PubMed  CAS  Google Scholar 

  • Li CY, Leopold AL, Sander GW, Shanks JV, Zhao L, Gibson SI (2013) The ORCA2 transcription factor plays a key role in regulation of the terpenoid indole alkaloid pathway. BMC Plant Biol 13:155

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Li CY, Leopold AL, Sander GW, Shanks JV, Zhao L, Gibson SI (2015) CrBPF1 overexpression alters transcript levels of terpenoid indole alkaloid biosynthetic and regulatory genes. Front Plant Sci 6:818

    PubMed  PubMed Central  Google Scholar 

  • Liu DH, Ren WW, Cui LJ, Zhang LD, Sun XF, Tang KX (2011) Enhanced accumulation of catharanthine and vindoline in Catharanthus roseus hairy roots by overexpression of transcriptional factor ORCA2. Afr J Biotechnol 10:3260

    Article  CAS  Google Scholar 

  • Liu W, Chen R, Chen M, Zhang H, Peng M, Yang C, Ming X, Lan X, Liao Z (2012) Tryptophan decarboxylase plays an important role in ajmalicine biosynthesis in Rauvolfia verticillata. Planta 236(1):239–250

    Article  CAS  PubMed  Google Scholar 

  • Liu J, Cai J, Wang R, Yang S (2017) Transcriptional regulation and transport of Terpenoid indole alkaloid in Catharanthus roseus: exploration of new research directions. Int J Mol Sci 18(1):53

    Article  CAS  Google Scholar 

  • López-Meyer M, Nessler CL (1997) Tryptophan decarboxylase is encoded by two autonomously regulated genes in Camptotheca acuminata which are differentially expressed during development and stress. Plant J 11:1167–1175

    Article  PubMed  Google Scholar 

  • Lorence A, Nessler CL (2004) Camptothecin, over four decades of surprising findings. Phytochemistry 65(20):2735–2749

    Article  CAS  PubMed  Google Scholar 

  • Ma X, Koepke J, Bayer A, Linhard V, Fritzsch G, Zhang B, Michel H, Stöckigt J (2004) Vinorine synthase from Rauvolfia: the first example of crystallization and preliminary X-ray diffraction analysis of an enzyme of the BAHD superfamily. Biochim Biophys Acta 1701(1–2):129–132

    Article  CAS  PubMed  Google Scholar 

  • Ma X, Panjikar S, Koepke J, Loris E, Stöckigt J (2006) The structure of Rauvolfia serpentina Strictosidine synthase is a novel six-bladed β-propeller fold in plant proteins. Plant Cell 18(4):907–920

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mehrotra S, Rahman LU, Kukreja AK (2010) An extensive case study of hairy-root cultures for enhanced secondary-metabolite production through metabolic-pathway engineering. Biotechnol Appl Biochem 56:161–172

    Article  CAS  PubMed  Google Scholar 

  • Mehrotra S, Srivastava V, Rahman LU, Kukreja AK (2013) Overexpression of a Catharanthus tryptophan decarboxylase (tdc) gene leads to enhanced terpenoid indole alkaloid (TIA) production in transgenic hairy root lines of Rauwolfia serpentina. Plant Cell Tissue Organ Cult 115:377–384

    Article  CAS  Google Scholar 

  • Mehrotra S, Goel MK, Srivastava V, Rahman LU (2015a) Hairy root biotechnology of Rauwolfia serpentina: a potent approach for the production of pharmaceutically important terpenoid indole alkaloids. Biotechnol Lett 37(2):253–263

    Article  PubMed  CAS  Google Scholar 

  • Mehrotra S, Srivastava V, Rahman LU, Kukreja AK (2015b) Hairy root Biotechnology-Indicative timeline to understand missing links and future outlook. Protoplasma 252(5):1189–1201

    Article  CAS  PubMed  Google Scholar 

  • Mehrotra S, Srivastava V, Goel MK, Kukreja AK (2016) Scale-up of Agrobacterium rhizogenes-mediated hairy root cultures of Rauwolfia serpentina: a persuasive approach for stable reserpine production. In: Jain S (ed) Protocols for in vitro cultures and secondary metabolite analysis of aromatic and medicinal plants, Methods in molecular biology, vol 1391, 2nd edn. Humana Press, New York

    Google Scholar 

  • Moreno-Valenzuela OA, Minero-García Y, Chan W, Mayer-Geraldo E, Carbajal E, Loyola-Vargas VM (2003) Increase in the indole alkaloid production and its excretion into the culture medium by calcium antagonists in Catharanthus roseus hairy roots. Biotechnol Lett 25:1345–1349

    Article  CAS  PubMed  Google Scholar 

  • Morgan JA, Shanks JV (2000) Determination of metabolic rate-limitations by precursor feeding in Catharanthus roseus hairy root cultures. J Biotechnol 79(2):137–145

    Article  CAS  PubMed  Google Scholar 

  • Morgan JA, Barney CS, Penn AH, Shanks JV (2000) Effects of buffered media upon growth and alkaloid production of Catharanthus roseus hairy roots. Appl Microbiol Biotechnol 53(3):262–265

    Article  CAS  PubMed  Google Scholar 

  • Namdeo AG, Sharma A (2012) HPLC analysis of camptothecin content in various parts of Nothapodytes foetida collected on different periods. Asian Pac J Trop Biomed 2(5):389–393

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Newman DJ, Cragg GM (2012) Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod 75:311–335

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • O’Connor SE, Maresh JJ (2006) Chemistry and biology of monoterpene indole alkaloid biosynthesis. Nat Prod Rep 23:532–547

    Article  PubMed  CAS  Google Scholar 

  • Oudin A, Mahroug S, Courdavault V, Hervouet N, Zelwer C, Rodriguez-Conception M, St-Pierre B, Burlat V (2007) Spatial distribution and hormonal regulation of gene products from methyl erythritol phosphate and monoterpene secoiridoid pathways in Catharanthus roseus. Plant Mol Biol 65:13–30

    Article  CAS  PubMed  Google Scholar 

  • Pan Q, Wang Q, Yuan F, Xing S, Zhao J, Choi YH, Verpoorte R, Tian Y, Wang G, Tang K (2012) Overexpression of ORCA3 and G10H in Catharanthus roseus plants regulated alkaloid biosynthesis and metabolism revealed by NMR-metabolomics. PLoS One 7:e43038

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Parr JA, Peerless ACJ, Hamill JD, Walton NJ, Robins RJ, Rhodes MJC (1988) Alkaloid production by transformed root cultures of Catharanthus roseus. Plant Cell Rep 7:309–312

    Article  CAS  PubMed  Google Scholar 

  • Peebles CA, Hong SB, Gibson SI, Shanks JV, San KY (2006) Effects of terpenoid precursor feeding on Catharanthus roseus hairy roots over-expressing the alpha or the alpha and beta subunits of anthranilate synthase. Biotechnol Bioeng 93(3):534–540

    Article  CAS  PubMed  Google Scholar 

  • Peebles CAM, Hughes EH, Shanks JV, San KY (2009) Transcriptional response of the terpenoid indole alkaloid pathway to the overexpression of ORCA3 along with jasmonic acid elicitation of Catharanthus roseus hairy roots over time. Metab Eng 11(2):76

    Article  CAS  PubMed  Google Scholar 

  • Peebles CA, Sander GW, Hughes EH, Peacock R, Shanks JV, San KY (2011) The expression of 1-deoxy-D-xylulose synthase and geraniol-10-hydroxylase or anthranilate synthase increases terpenoid indole alkaloid accumulation in Catharanthus roseus hairy roots. Metab Eng 13(2):234–240

    Article  CAS  PubMed  Google Scholar 

  • Rajasekharan PE, Abdul Kareem VK, Kavitha P (2011) Enhancement of Camptothecin production in N. Nimmoniana, graham an anticancerous medicinal plant: current and future perspective. IUP J Biotechnol 5(2):7–29

    Google Scholar 

  • Raveendran VV (2015) Camptothecin-discovery, clinical perspectives and biotechnology. Nat Prod Chem Res 3:175

    Google Scholar 

  • Rijhwani SK, Shanks JV (1998) Effect of elicitor dosage and exposure time on biosynthesis of indole alkaloids by Catharanthus roseus hairy root cultures. Biotechnol Prog 14:442–449

    Article  CAS  PubMed  Google Scholar 

  • Roja G (2006) Comparative studies on the camptothecin content from Nothapodytes foetida and Ophiorrhiza species. Nat Prod Res 20(1):85–88

    Article  CAS  PubMed  Google Scholar 

  • Ruiz-May E, Galaz-Ávalos RM, Loyola-Vargas VM (2009) Differential secretion and accumulation of terpene indole alkaloids in hairy roots of Catharanthus roseus treated with methyl jasmonate. Mol Biotechnol 41:278

    Article  CAS  PubMed  Google Scholar 

  • Salim V, De Luca V (2013) Towards complete elucidation of monoterpene indole alkaloid biosynthesis pathway: Catharanthus roseus as a pioneer system. Adv Bot Res 68:1–37

    Article  CAS  Google Scholar 

  • Seca AM, Pinto DC (2018) Plant secondary metabolites as anticancer agents: successes in clinical trials and therapeutic application. Int J Mol Sci 19(1):263

    Article  PubMed Central  CAS  Google Scholar 

  • Sim SJ, Chang HN, Liu JR, Jung KH (1994) Production and secretion of indole alkaloids in hairy root cultures of Catharanthus roseus: effects of in situ adsorption, fungal elicitation and permeabilization. J Ferment Bioeng 78:229–234

    Article  CAS  Google Scholar 

  • Singh TP, Singh OM (2018) Recent progress in biological activities of indole and indole alkaloids. Mini Rev Med Chem 18(1):9–25

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Sirikantaramas S, Asano T, Sudo H, Yamazaki M, Saito K (2007b) Camptothecin: therapeutic potential and biotechnology. Curr Pharm Biotechnol 8(4):196–202

    Article  CAS  PubMed  Google Scholar 

  • Srivastava V, Mehrotra S, Verma PK (2017) Biotechnological interventions for production of therapeutic secondary metabolites using hairy root cultures of medicinal plants. In: Dubey SK, Pandey A, Sangwan RS (eds) Current developments in biotechnology and bioengineering. Elsevier, New York, pp 259–282

    Chapter  Google Scholar 

  • Sudha CG, Reddy Obul B, Ravishankar GA, Seeni S (2003) Production of ajmalicine and ajmaline in hairy root cultures of Rauvolfia micrantha Hook f., a rare and endemic medicinal plant. Biotechnol Lett 5(8):631–636

    Article  Google Scholar 

  • Sudo H, Yamakawa T, Yamazaki M, Aimi N, Saito K (2004) Bioreactor production of camptothecin by hairy root cultures of Ophiorrhiza pumila. Biotechnol Lett 24(5):359–363

    Article  Google Scholar 

  • Sun J, Peebles CAM (2016) The elucidation and metabolic engineering of Terpenoid indole alkaloid pathway in Catharanthus roseus hairy roots. In: Jha S (ed) Transgenesis and secondary metabolism, Reference series in phytochemistry. Springer, Cham

    Google Scholar 

  • Sun J, Zhao L, Shao Z, Shanks J, Peebles CAM (2018) Expression of tabersonine 16-hydroxylase and 16-hydroxytabersonine-O-methyltransferase in Catharanthus roseus hairy roots. Biotechnol Bioeng 115(3):673–683

    Article  CAS  PubMed  Google Scholar 

  • Suttipanta N, Pattanaik S, Kulshrestha M, Patra B, Singh SK, Yuan L (2011) The transcription factor CrWRKY1 positively regulates the Terpenoid indole alkaloid biosynthesis in Catharanthus roseus. Plant Physiol 157:2081–2093

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Talano MA, Oller AL, González PS, Agostini E (2012) Hairy roots, their multiple applications and recent patents. Recent Pat Biotechnol 6(2):115–133

    Article  CAS  PubMed  Google Scholar 

  • Thakore D, Srivastava AK, Sinha AK (2017) Mass production of Ajmalicine by bioreactor cultivation of hairy roots of Catharanthus roseus. Biochem Eng J 119:84–91

    Article  CAS  Google Scholar 

  • Thomas CJ, Rahier NJ, Hecht SM (2004) Camptothecin: current perspectives. Bioorg Med Chem 12(7):1585–1604

    Article  CAS  PubMed  Google Scholar 

  • Tikhomiroff C, Jolicoeur M (2002) Screening of Catharanthus roseus secondary metabolites by high-performance liquid chromatography. J Chromatogr A 955:87–93

    Article  CAS  PubMed  Google Scholar 

  • Toivonen L, Balsevich J, Kurz WG (1989) Indole alkaloid production by hairy root cultures of Catharanthus roseus. Plant Cell Tissue Org Cult 18:79–93

    Article  CAS  Google Scholar 

  • Toivonen L, Ojala M, Kauppinen V (1991) Studies on the optimization of growth and indole alkaloid production by hairy root cultures of Catharanthus roseus. Biotechnol Bioeng 37(7):673–680

    Article  CAS  PubMed  Google Scholar 

  • Udomsom N, Rai A, Suzuki H, Okuyama J, Imai R, Mori T, Nakabayashi R, Saito K, Yamazaki M (2016) Function of AP2/ERF transcription factors involved in the regulation of specialized metabolism in Ophiorrhiza pumila revealed by transcriptomics and metabolomics. Front Plant Sci 7:1861

    Article  PubMed  PubMed Central  Google Scholar 

  • Vantourout JC, Isidro-Liobe A, Watson AJB (2017) Conventional and bioinspired syntheses of Monoterpenoid indole alkaloids. In: Rahman A (ed) Studies in natural product chemistry, vol 55. Elsevier, Amsterdam, pp 1–29

    Google Scholar 

  • Vazquez-Flota F, Moreno-Valenzuela O, Miranda-Ham ML, Coello-Coello J, Loyola-Vargas V (1994) Catharanthine and ajmalicine synthesis in Catharanthus roseus hairy root cultures. Plant Cell Tissue Organ Cult 38:273–279

    Article  CAS  Google Scholar 

  • Venditto VJ, Simanek EE (2010) Cancer therapies utilizing the camptothecins: a review of the in vivo literature. Mol Pharm 7:307–349

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Verma P, Mathur AK, Shanker K (2012) Growth, alkaloid production, rol genes integration, bioreactor up-scaling and plant regeneration studies in hairy root lines of Catharanthus roseus. Plant Biosyst 146:27–40

    Article  Google Scholar 

  • Wang CT, Liu H, Gao XS, Zhang HX (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 

  • Wu F, Kerčmar P, Zhang C, Stöckigt J (2016) Chapter one – Sarpagan-Ajmalan-type indoles: biosynthesis, structural biology, and chemo-enzymatic significance. Alkaloids Chem Biol 76:1–61

    Article  CAS  PubMed  Google Scholar 

  • Yamazaki Y, Sudo H, Yamazaki M, Aimi N, Saito K (2003) Camptothecin biosynthetic genes in hairy roots of Ophiorrhiza pumila: cloning, characterization and differential expression in tissues and by stress compounds. Plant Cell Physiol 44(4):395–403

    Article  CAS  PubMed  Google Scholar 

  • 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 anti-cancer alkaloid camptothecin and anthraquinones. Plant Cell Physiol 54(5):686–696. https://doi.org/10.1093/pcp/pct040

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ya-ut P, Sukrong S, Chareonsap PP (2011) Micropropagation and hairy root culture of Ophiorrhiza alata Craib for camptothecin production. Biotechnol Lett 33(12):2519–2526

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

V.S. acknowledges Central University of Jammu for providing the work facility and also thankful to UGC, India for Start- Up research grant. S.M. is thankful to Science & Engineering Research Board (SERB, India) for NPDF (PDF/2016/002133) fellowship.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Vikas Srivastava .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Mehrotra, S., Mishra, S., Srivastava, V. (2018). Hairy Root Cultures for Monoterpene Indole Alkaloid Pathway: Investigation and Biotechnological Production. In: Srivastava, V., Mehrotra, S., Mishra, S. (eds) Hairy Roots. Springer, Singapore. https://doi.org/10.1007/978-981-13-2562-5_5

Download citation

Publish with us

Policies and ethics