Skip to main content
SpringerLink
Log in

Production of Indole Alkaloids in Catharanthus roseus L. Hairy Root Cultures

  • Chapter
  • First Online:
Production of Plant Derived Natural Compounds through Hairy Root Culture

Abstract

Hairy root cultures of Catharanthus roseus L. induced by Agrobacterium rhizogenes have been studied extensively by several research groups for the production of the valuable indole alkaloids. Due to the pharmaceutical importance and the low content of indole alkaloids in this plant, C. roseus became one of the best-studied medicinal plants. Various biotechnological approaches, such as pathway engineering, precursor feeding and scaling up in bioreactors, etc., have been explored to improve the production of secondary metabolites from this plant species. The hairy roots proved to be a sustainable source for the economic mass in vitro production of indole alkaloids such as pharmaceutically valuable anticancer alkaloids: vinblastine and vincristine. This chapter provides a comprehensive account of the hairy root cultures of C. roseus L. and various biotechnological methods used to elevate the production of pharmaceutically important indole alkaloids. The chapter also indicates how biotechnological endeavors might improve the future progress of research for production of alkaloids using C. roseus L. hairy roots.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
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

Abbreviations

AP2:

APETALA2

AS:

Anthranilate synthase

CrBPF1:

C. roseus box P-binding factor 1 homologue

CrMYC:

C. roseus MYC transcription factor

CrPrx:

Apoplastic peroxidase gene

CrWRKY:

C. roseus WRKY transcription factor

DAT:

Deacetylvindoline 4-O-acetyltransferase

DXS:

1-Deoxy-D-xylulose synthase

G10H:

Geraniol 10-hydroxylase

GmMYBZ2:

Soybean transcription factor MYBZ2

JA:

Jasmonic acid

MeJA:

Methyl jasmonate

ORCA:

Octadecanoid-responsive Catharanthus AP2-domain

STR:

Strictosidine synthase

TDC:

Tryptophan decarboxylase

TIAs:

Terpenoid indole alkaloid

ZCT:

Zinc-finger Catharanthus transcription factor

References

  • Almagro L, Perez AL, Pedreño M (2011a) New method to enhance ajmalicine production in Catharanthus roseus cell cultures based on the use of cyclodextrins. Biotechnol Lett 33:381–385

    Article  CAS  PubMed  Google Scholar 

  • Almagro L, Sabater-Jara AB, Belchí-Navarro S, Fernández-Pérez F, Bru R, Pedreño MA (2011b) Effect of UV light on secondary metabolite biosynthesis in plant cell cultures elicited with cyclodextrins and methyljasmonate. Plants Environ Intech: 115–136

    Google Scholar 

  • Almagro L, Gutierrez J, Pedreño MA, Sottomayor M (2014) Synergistic and additive influence of cyclodextrins and methyl jasmonate on the expression of the terpenoid indole alkaloid pathway genes and metabolites in Catharanthus roseus cell cultures. Plant Cell Tissue Organ Cult (PCTOC) 119:543–551

    Article  CAS  Google Scholar 

  • Almagro L, Fernández-Pérez F, Pedreño MA (2015) Indole alkaloids from Catharanthus roseus: bioproduction and their effect on human health. Molecules 20:2973–3000

    Article  PubMed  CAS  Google Scholar 

  • Ayora-Talavera T, Chappell J, Lozoya-Gloria E, Loyola-Vargas VM (2002) Overexpression in Catharanthus roseus hairy roots of a truncated hamster 3-hydroxy-3-methylglutaryl-CoA reductase gene. Appl Biochem Biotechnol 97:135–145

    Article  CAS  PubMed  Google Scholar 

  • Bailey C, Nicholson H (1990) Optimal temperature control for a structured model of plant cell culture. Biotechnol Bioeng 35:252–259

    Article  CAS  PubMed  Google Scholar 

  • Banerjee S, Singh S, Rahman LU (2012) Biotransformation studies using hairy root cultures—a review. Biotechnol Adv 30:461–468

    Article  CAS  PubMed  Google Scholar 

  • Barkat MA, Abul H, Rahman MA (2017) Agricultural, pharmaceutical, and therapeutic interior of Catharanthus roseus (L.) In: Don G (ed) Catharanthus roseus. Springer International Publishing, Basel, pp 71–100

    Chapter  Google Scholar 

  • Batra J, Dutta A, Singh D, Kumar S, Sen J (2004) Growth and terpenoid indole alkaloid production in Catharanthus roseus hairy root clones in relation to left-and right-termini-linked Ri T-DNA gene integration. Plant Cell Rep 23:148–154

    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 41:581–592

    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 

  • Bourgaud F, Gravot A, Milesi S, Gontier E (2001) Production of plant secondary metabolites: a historical perspective. Plant Sci 161:839–851

    Article  CAS  Google Scholar 

  • Bruni R, Sacchetti G (2009) Factors affecting polyphenol biosynthesis in wild and field grown St. John’s Wort (Hypericum perforatum L. Hypericaceae/Guttiferae). Molecules 14:682–725

    Article  CAS  PubMed  Google Scholar 

  • Chang K, Qiu F, Chen M, Zeng L, Liu X, Yang C, Lan X, Wang Q, Liao Z (2014) Engineering the MEP pathway enhanced ajmalicine biosynthesis. Biotechnol Appl Biochem 61:249–255

    Article  CAS  PubMed  Google Scholar 

  • Chilton M-D, Tepfer DA, Petit A, David C, Casse-Delbart F, Tempé J (1982) Agrobacterium rhizogenes inserts T-DNA into the genomes of the host plant root cells. Nature 295(5848):432–434

    Article  CAS  Google Scholar 

  • Christey MC (2001) Use of Ri-mediated transformation for production of transgenic plants. In Vitro Cell Dev Biol Plant 37:687–700

    Article  CAS  Google Scholar 

  • Chung IM, Hong SB, Peebles CA, Kim J, San KY (2007) Effect of the engineered indole pathway on accumulation of phenolic compounds in Catharanthus roseus hairy roots. Biotechnol Prog 23:327–332

    Article  CAS  PubMed  Google Scholar 

  • Deus-Neumann B, Zenk M (1984) Instability of indole alkaloid production in Catharanthus roseus cell suspension cultures. Planta Med 50:427–431

    Article  CAS  PubMed  Google Scholar 

  • DiCosmo F, Misawa M (1995) Plant cell and tissue culture: alternatives for metabolite production. Biotechnol Adv 13:425–453

    Article  CAS  PubMed  Google Scholar 

  • Dutta A, Batra J, Pandey-Rai S, Singh D, Kumar S, Sen J (2005) Expression of terpenoid indole alkaloid biosynthetic pathway genes corresponds to accumulation of related alkaloids in Catharanthus roseus (L.) G. Don. Planta 220:376–383

    Article  CAS  PubMed  Google Scholar 

  • Dutta A, Sen J, Deswal R (2007) Downregulation of terpenoid indole alkaloid biosynthetic pathway by low temperature and cloning of a AP2 type C-repeat binding factor (CBF) from Catharanthus roseus (L). G Don. Plant Cell Rep 26:1869–1878

    Article  CAS  PubMed  Google Scholar 

  • Eilert U, DeLuca V, Kurz W, Constabel F (1987) Alkaloid formation by habituated and tumorous cell suspension cultures of Catharanthus roseus. Plant Cell Rep 6:271–274

    Article  CAS  PubMed  Google Scholar 

  • El-Sayed M, Verpoorte R (2002) Effect of phytohormones on growth and alkaloid accumulation by a Catharanthus roseus cell suspension cultures fed with alkaloid precursors tryptamine and loganin. Plant Cell Tissue Organ Cult 68:265–270

    Article  CAS  Google Scholar 

  • El-Sayed M, Verpoorte R (2007) Catharanthus terpenoid indole alkaloids: biosynthesis and regulation. Phytochem Rev 6:277–305

    Article  CAS  Google Scholar 

  • El-Sayed M, Choi YH, Frederich M, Roytrakul S, Verpoorte R (2004) Alkaloid accumulation in Catharanthus roseus cell suspension cultures fed with stemmadenine. Biotechnol Lett 26:793–798

    Article  CAS  PubMed  Google Scholar 

  • Fujita Y, Hara Y, Suga C, Morimoto T (1981) Production of shikonin derivatives by cell suspension cultures of Lithospermum erythrorhizon. Plant Cell Rep 1:61–63

    Article  CAS  PubMed  Google Scholar 

  • Gaines J (2004) Increasing alkaloid production from Catharanthus roseus suspensions through methyl jasmonate elicitation. Pharm Eng 24:106–123

    Google Scholar 

  • Gantet P, Memelink J (2002) Transcription factors: tools to engineer the production of pharmacologically active plant metabolites. Trends Pharmacol Sci 23:563–569

    Article  CAS  PubMed  Google Scholar 

  • Garnier F, Hamdi S, Label P, Rideau M (1999) Genetic transformation of Catharanthus roseus (periwinkle). In: Transgenic medicinal plants. Springer, Berlin, pp 88–102

    Chapter  Google Scholar 

  • Georgiev MI, Pavlov AI, Bley T (2007) Hairy root type plant in vitro systems as sources of bioactive substances. Appl Microbiol Biotechnol 74:1175

    Article  CAS  PubMed  Google Scholar 

  • Giri A, Narasu ML (2000) Transgenic hairy roots: recent trends and applications. Biotechnol Adv 18:1–22

    Article  CAS  PubMed  Google Scholar 

  • Goldhaber-Pasillas GD, Mustafa NR, Verpoorte R (2014) Jasmonic acid effect on the fatty acid and terpenoid indole alkaloid accumulation in cell suspension cultures of Catharanthus roseus. Molecules 19:10242–10260

    Article  PubMed  CAS  Google Scholar 

  • Gray DE, Pallardy SG, Garrett H, Rottinghaus GE (2003) Acute drought stress and plant age effects on alkamide and phenolic acid content in purple coneflower roots. Planta Med 69:50–55

    Article  CAS  PubMed  Google Scholar 

  • Guillon S, Tremouillaux-Guiller J, Pati PK, Rideau M, Gantet P (2006a) Harnessing the potential of hairy roots: dawn of a new era. Trends Biotechnol 24:403–409

    Article  CAS  PubMed  Google Scholar 

  • Guillon S, Trémouillaux-Guiller J, Pati PK, Rideau M, Gantet P (2006b) Hairy root research: recent scenario and exciting prospects. Curr Opin Plant Biol 9:341–346

    Article  CAS  PubMed  Google Scholar 

  • Guillon S, Trémouillaux-Guiller J, Pati PK, Gantet P (2008) Hairy roots: a powerful tool for plant biotechnological advances. In: Bioactive molecules and medicinal plants. Springer, Berlin, pp 271–283

    Chapter  Google Scholar 

  • Hanafy M, Matter M, Asker M, Rady M (2016) Production of indole alkaloids in hairy root cultures of Catharanthus roseus L. and their antimicrobial activity. S Afr J Bot 105:9–18

    Article  CAS  Google Scholar 

  • He S, Zhu J, Zi J, Zhou P, Liang J, Yu R (2015) A novel terpenoid indole alkaloid derived from catharanthine via biotransformation by suspension-cultured cells of Catharanthus roseus. Biotechnol Lett 37:2481–2487

    Article  CAS  PubMed  Google Scholar 

  • Heijden R, Jacobs DI, Snoeijer W, Hallard D, Verpoorte R (2004) The Catharanthus alkaloids: pharmacognosy and biotechnology. Curr Med Chem 11:607–628

    Article  Google Scholar 

  • Honda Y, Inaoka H, Takei A, Sugimura Y, Otsuji K (1996) Extracellular polysaccharides produced by tuberose callus. Phytochemistry 41:1517–1521

    Article  CAS  PubMed  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, Shanks JV (2002) Metabolic engineering of plants for alkaloid production. Metab Eng 4:41–48

    Article  CAS  PubMed  Google Scholar 

  • Hughes EH, Hong S-B, Gibson SI, Shanks JV, San K-Y (2004a) 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 

  • Hughes EH, Hong SB, Gibson SI, Shanks JV, San KY (2004b) 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 

  • Islas I, Loyola-Vargas VM, de Lourdes Miranda-Ham M (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 

  • Iwase A, Aoyagi H, Ohme-Takagi M, Tanaka H (2005) Development of a novel system for producing ajmalicine and serpentine using direct culture of leaves in Catharanthus roseus intact plant. J Biosci Bioeng 99:208–215

    Article  CAS  PubMed  Google Scholar 

  • Jaggi M, Kumar S, Sinha AK (2011) Overexpression of an apoplastic peroxidase gene CrPrx in transgenic hairy root lines of Catharanthus roseus. Appl Microbiol Biotechnol 90:1005–1016

    Article  CAS  PubMed  Google Scholar 

  • Jung K, Kwak S, Kim S, Lee H, Choi C, Liu J (1992) Improvement of the catharanthine productivity in hairy root cultures of Catharanthus roseus by using monosaccharides as a carbon source. Biotechnol Lett 14:695–700

    Article  CAS  Google Scholar 

  • Jung KH, Kwak SS, Choi CY, Liu JR (1995) An interchangeable system of hairy root and cell suspension cultures of Catharanthus roseus for indole alkaloid production. Plant Cell Rep 15:51–54

    Article  CAS  PubMed  Google Scholar 

  • Kaeppler S, Phillips R (1993) DNA methylation and tissue culture-induced variation in plants. In Vitro Cell Dev Biol Plant 29:125–130

    Article  Google Scholar 

  • Kalidass C, Mohan VR, Daniel A (2009) Effect of auxin and cytokinin on vincristine production by callus cultures of Catharanthus roseus L.(apocynaceae). Trop Subtrop Agroecosyst 12:283–288

    Google Scholar 

  • Lee-Parsons CW (2007) Gas composition strategies for the successful scale-up of Catharanthus roseus cell cultures for the production of ajmalicine. Phytochem Rev 6:419–433

    Article  CAS  Google Scholar 

  • Li J, Last RL (1996) The Arabidopsis thaliana trp5 mutant has a feedback-resistant anthranilate synthase and elevated soluble tryptophan. Plant Physiol 110:51–59

    Article  CAS  PubMed  PubMed Central  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 27:625–630

    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 

  • Liu D-H, Ren W-W, Cui L-J, Zhang L-D, Sun X-F, Tang K-X (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 

  • Lounasmaa M, Galambos J (1989) Indole alkaloid production in Catharanthus roseus cell suspension cultures. In: Fortschritte der Chemie organischer Naturstoffe/Progress in the chemistry of organic natural products. Springer, Vienna, pp 89–115

    Chapter  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 

  • Malik S, Bhushan S, Sharma M, Ahuja PS (2016) Biotechnological approaches to the production of shikonins: a critical review with recent updates. Crit Rev Biotechnol 36:327–340

    Article  CAS  PubMed  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 

  • Meijer A (1993) Regulation of enzymes and genes involved in terpenoid indole alkaloid biosynthesis in Catharanthus roseus. J Plant Res special issue 3:145–164

    Google Scholar 

  • Memelink J, Gantet P (2007) Transcription factors involved in terpenoid indole alkaloid biosynthesis in Catharanthus roseus. Phytochem Rev 6:353–362

    Article  CAS  Google Scholar 

  • Misra N, Luthra R, Kumar S (1996) Enzymology of indole alkaloid biosynthesis in Catharanthus roseus. Indian J Biochem Biophys 33:261–273

    CAS  PubMed  Google Scholar 

  • Mitra A, Khan B, Rawal S (1997) Photoautotrophic shoot culture: an economical alternative for the production of total alkaloid from Catharanthus roseus (L.) G. Don. Curr Sci 73:608–609

    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 (1999) Inhibitor studies of tabersonine metabolism in C. roseus hairy roots. Phytochemistry 51:61–68

    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 79:137–145

    Article  CAS  PubMed  Google Scholar 

  • Morgan J, Barney C, Penn A, Shanks J (2000) Effects of buffered media upon growth and alkaloid production of Catharanthus roseus hairy roots. Appl Microbiol Biotechnol 53:262–265

    Article  CAS  PubMed  Google Scholar 

  • Mujib A, Ilah A, Aslam J, Fatima S, Siddiqui ZH, Maqsood M (2012) Catharanthus roseus alkaloids: application of biotechnology for improving yield. Plant Growth Regul 68:111–127

    Article  CAS  Google Scholar 

  • Noble RL (1990) The discovery of the vinca alkaloids—chemotherapeutic agents against cancer. Biochem Cell Biol 68:1344–1351

    Article  CAS  PubMed  Google Scholar 

  • Nuutila A, Toivonen L, Kauppinen V (1994) Bioreactor studies on hairy root cultures of Catharanthus roseus: comparison of three bioreactor types. Biotechnol Tech 8:61–66

    Article  CAS  Google Scholar 

  • O’Keefe BR, Mahady GB, Gills JJ, Beecher CW, Schilling AB (1997) Stable vindoline production in transformed cell cultures of Catharanthus roseus. J Nat Prod 60:261–264

    Article  Google Scholar 

  • Ono NN, Tian L (2011) The multiplicity of hairy root cultures: prolific possibilities. Plant Sci 180:439–446

    Article  CAS  PubMed  Google Scholar 

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

    Article  Google Scholar 

  • Pandiangan D, WennyTilaar NN, Wahyudi L (2015) Relations between catharanthine content enhancement with the other associated secondary metabolites in Catharanthus roseus cell culture that treated tryptophan. Int J Sci Res 4:2208–2212

    Google Scholar 

  • Patel H, Krishnamurthy R (2013) Elicitors in plant tissue culture. J Pharmacogn Phytochem 2:60–65

    CAS  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 93:534–540

    Article  CAS  PubMed  Google Scholar 

  • Peebles CA, Gibson SI, Shanks JV, San KY (2007) Characterization of an ethanol-inducible promoter system in Catharanthus roseus hairy roots. Biotechnol Prog 23:1258–1260

    Article  CAS  PubMed  Google Scholar 

  • Peebles CA, Hughes EH, Shanks JV, San K-Y (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 11:76–86

    Article  CAS  PubMed  Google Scholar 

  • Peebles CA, Sander GW, Hughes EH, Peacock R, Shanks JV, San K-Y (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 13:234–240

    Article  CAS  PubMed  Google Scholar 

  • Phillips RL, Kaeppler SM, Olhoft P (1994) Genetic instability of plant tissue cultures: breakdown of normal controls. Proc Natl Acad Sci 91:5222–5226

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Poulsen C, Bongaerts RJ, Verpoorte R (1993) Purification and characterization of anthranilate synthase from Catharanthus roseus. Eur J Biochem 212:431–440

    Article  CAS  PubMed  Google Scholar 

  • Radman R, Saez T, Bucke C, Keshavarz T (2003) Elicitation of plants and microbial cell systems. Biotechnol Appl Biochem 37:91–102

    Article  CAS  PubMed  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 

  • Rizvi NF, Weaver JD, Cram EJ, Lee-Parsons CW (2016) Silencing the transcriptional repressor, ZCT1, illustrates the tight regulation of terpenoid indole alkaloid biosynthesis in Catharanthus roseus hairy roots. PLoS One 11:e0159712

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Rodriguez S, Compagnon V, Crouch NP, St-Pierre B, De Luca V (2003) Jasmonate-induced epoxidation of tabersonine by a cytochrome P-450 in hairy root cultures of Catharanthus roseus. Phytochemistry 64:401–409

    Article  CAS  PubMed  Google Scholar 

  • Roepke J, Salim V, Wu M, Thamm AM, Murata J, Ploss K, Boland W, De Luca V (2010) Vinca drug components accumulate exclusively in leaf exudates of Madagascar periwinkle. Proc Natl Acad Sci 107:15287–15292

    Article  CAS  PubMed  PubMed Central  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 

  • Salma U, Rahman M, Islam S, Haque N, Jubair T, Haque A, Mukti I (2008) The influence of different hormone concentration and combination on callus induction and regeneration of Rauwolfia serpentina L. Benth. Pak J Biol Sci: PJBS 11:1638–1641

    Article  CAS  PubMed  Google Scholar 

  • Schlatmann J, Ten Hoopen H, Heijnen J (1992) Optimization of the medium composition for alkaloid production by Catharanthus roseus using statistical experimental designs. Meded Fac Landbouwwet Rijksuniv Gent (Belgium) 57:1567–1569

    CAS  Google Scholar 

  • Seigler DS (2001) Plant secondary metabolism. JSTOR:205

    Google Scholar 

  • Senoussi M, Creche J, Rideau M (2007) Relation between hypoxia and alkaloid accumulation in Catharanthus roseus cell suspension. J Appl Sci Res 3:287–290

    CAS  Google Scholar 

  • Shanks JV, Bhadra R, Morgan J, Rijhwani S, Vani S (1998) Quantification of metabolites in the indole alkaloid pathways of Catharanthus roseus: implications for metabolic engineering. Biotechnol Bioeng 58:333–338

    Article  CAS  PubMed  Google Scholar 

  • Shimomura K, Sudo H, Saga H, Kamada H (1991) Shikonin production and secretion by hairy root cultures of Lithospermum erythrorhizon. Plant Cell Rep 10:282–285

    Article  CAS  PubMed  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 BK, Siehl DL, Connelly JA (eds) (1991) Shikimate pathway: why does it mean so much to so many?

    Google Scholar 

  • Sirvent TM, Krasnoff SB, Gibson DM (2003) Induction of hypericins and hyperforins in Hypericum perforatum in response to damage by herbivores. J Chem Ecol 29:2667–2681

    Article  CAS  PubMed  Google Scholar 

  • Srivastava S, Srivastava AK (2007) Hairy root culture for mass-production of high-value secondary metabolites. Crit Rev Biotechnol 27:29–43

    Article  CAS  PubMed  Google Scholar 

  • Sun J, Peebles CA (2016) Engineering overexpression of ORCA3 and strictosidine glucosidase in Catharanthus roseus hairy roots increases alkaloid production. Protoplasma 253:1255–1264

    Article  CAS  PubMed  Google Scholar 

  • Sun M, Zeng J (2005) A study on the hairy root culture and antitumor alkaloids production of Catharanthus roseus. Zhongguo Zhong yao za zhi= Zhongguo zhongyao zazhi=. China J Chin Mater Med 30(741–743):755

    Google Scholar 

  • Sun J, Ma L, San KY, Peebles CA (2017) Still stable after 11 years: a Catharanthus roseus Hairy root line maintains inducible expression of anthranilate synthase. Biotechnol Prog 33:66–69

    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 

  • Svoboda GH (1966) The current status of research on the alkaloids of Vinca rosea Linn. (Catharanthus roseus G. Don). In: Proceedings first symposium European Cancer Chemotherapy Group (G. E.C.A.), Paris, June. 1965, Excerpta Medica International Congress Series No. 106, p. 9–28, Amsterdam, pp 9–28

    Google Scholar 

  • Tang K, Liu D, Wang Y, Cui L, Ren W, Sun X (2011) Overexpression of transcriptional factor ORCA3 increases the accumulation of catharanthine and vindoline in Catharanthus roseus hairy roots. Russ J Plant Physiol 58:415–422

    Article  CAS  Google Scholar 

  • Thakore D, Srivastava A, Sinha A (2012) Enhanced production of antihypertensive drug ajmalicine in transformed hairy root culture of Catharanthus roseus by application of stress factors in statistically optimized medium. In: Chemistry of phytopotentials: health, energy and environmental perspectives. Springer, Berlin, pp 39–42

    Chapter  Google Scholar 

  • Thakore D, Srivastava A, Sinha A (2013) Yield enhancement strategies for enhancement of indole alkaloids in hairy root cultures of Catharanthus roseus. Int J Chem Eng Appl 4:153

    CAS  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 

  • Tian L (2015) Using hairy roots for production of valuable plant secondary metabolites. In: Filaments in bioprocesses. Springer, Basel, pp 275–324

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

    Article  CAS  PubMed  Google Scholar 

  • Toivonen L, Laakso S, Rosenqvist H (1992) The effect of temperature on hairy root cultures of Catharanthus roseus: growth, indole alkaloid accumulation and membrane lipid composition. Plant Cell Rep 11:395–399

    CAS  PubMed  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 

  • Vazquez-Flota F, Monforte-Gonzalez M, Mendez-Zeel M, Minero-Garcia Y, Loyola-Vargas VM (2000) Effects the of nitrogen source on alkaloid metabolism in callus culture of Catharanthus roseus (L.) G Don. Phyton 66:155–164

    CAS  Google Scholar 

  • Verma AK, Singh R, Singh S (2012) Improved alkaloid content in callus culture of Catharanthus roseus. Bot Serbica 36:123–130

    Google Scholar 

  • Verma P, Khan SA, Mathur AK, Shanker K, Kalra A (2014) Fungal endophytes enhanced the growth and production kinetics of Vinca minor hairy roots and cell suspensions grown in bioreactor. Plant Cell Tissue Organ Cult (PCTOC) 118:257–268

    Article  CAS  Google Scholar 

  • Verma P, Sharma A, Khan SA, Shanker K, Mathur AK (2015) Over-expression of Catharanthus roseus tryptophan decarboxylase and strictosidine synthase in rol gene integrated transgenic cell suspensions of Vinca minor. Protoplasma 252:373–381

    Article  CAS  PubMed  Google Scholar 

  • Verpoorte R, Van Der Heijden R, Ten Hoopen H, Memelink J (1999) Metabolic engineering of plant secondary metabolite pathways for the production of fine chemicals. Biotechnol Lett 21:467–479

    Article  CAS  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 29:887–894

    Article  CAS  PubMed  Google Scholar 

  • Wang L, He H-P, Di Y-T, Zhang Y, Hao X-J (2012) Catharoseumine, a new monoterpenoid indole alkaloid possessing a peroxy bridge from Catharanthus roseus. Tetrahedron Lett 53:1576–1578

    Article  CAS  Google Scholar 

  • Wesołowska A, Grzeszczuk M, Wilas J, Kulpa D (2016) Gas chromatography-mass spectrometry (GC-MS) analysis of indole alkaloids isolated from Catharanthus roseus (L.) G. Don cultivated conventionally and derived from in vitro cultures. Notulae Botanicae Horti Agrobotanici Cluj-Napoca 44:100–106

    Article  CAS  Google Scholar 

  • Whitmer S, van der Heijden R, Verpoorte R (2002) Effect of precursor feeding on alkaloid accumulation by a tryptophan decarboxylase over-expressing transgenic cell line T22 of Catharanthus roseus. J Biotechnol 96:193–203

    Article  CAS  PubMed  Google Scholar 

  • Whitmer S, Canel C, van der Heijden R, Verpoorte R (2003) Long-term instability of alkaloid production by stably transformed cell lines of Catharanthus roseus. Plant Cell Tissue Organ Cult 74:73–80

    Article  CAS  Google Scholar 

  • Wilson SA, Roberts SC (2014) Metabolic engineering approaches for production of biochemicals in food and medicinal plants. Curr Opin Biotechnol 26:174–182

    Article  CAS  PubMed  Google Scholar 

  • Xiang B-B, Zhu Y-R, Wang W-J, Bai Y-L, Wang Y (2011) Cell line screening of Catharanthus roseus for high yield production of ajmalicine. J Med Plant Res 5:420–425

    Article  CAS  Google Scholar 

  • Zhao J, Zhu W-H, Hu Q (2000) Enhanced ajmalicine production in Catharanthus roseus cell cultures by combined elicitor treatment: from shake-flask to 20-l airlift bioreactor. Biotechnol Lett 22:509–514

    Article  CAS  Google Scholar 

  • Zhao J, Zhu W-H, Hu Q (2001a) Effects of light and plant growth regulators on the biosynthesis of vindoline and other indole alkaloids in Catharanthus roseus callus cultures. Plant Growth Regul 33:43–49

    Article  CAS  Google Scholar 

  • Zhao J, Zhu W-H, Hu Q, Guo Y-Q (2001b) Compact callus cluster suspension cultures of Catharanthus roseus with enhanced indole alkaloid biosynthesis. In Vitro Cell Dev Biol Plant 37:68–72

    Article  CAS  Google Scholar 

  • Zhong J-J (2002) Plant cell culture for production of paclitaxel and other taxanes. J Biosci Bioeng 94:591–599

    Article  CAS  PubMed  Google Scholar 

  • Zhou M-L, Zhu X-M, Shao J-R, Wu Y-M, Tang Y-X (2010) Transcriptional response of the catharanthine biosynthesis pathway to methyl jasmonate/nitric oxide elicitation in Catharanthus roseus hairy root culture. Appl Microbiol Biotechnol 88:737–750

    Article  CAS  PubMed  Google Scholar 

  • Zhou M-L, Hou H-L, Zhu X-M, Shao J-R, Wu Y-M, Tang Y-X (2011) Soybean transcription factor GmMYBZ2 represses catharanthine biosynthesis in hairy roots of Catharanthus roseus. Appl Microbiol Biotechnol 91:1095–1105

    Article  CAS  PubMed  Google Scholar 

  • Zhou P, Yang J, Zhu J, He S, Zhang W, Yu R, Zi J, Song L, Huang X (2015) Effects of β-cyclodextrin and methyl jasmonate on the production of vindoline, catharanthine, and ajmalicine in Catharanthus roseus cambial meristematic cell cultures. Appl Microbiol Biotechnol 99:7035–7045

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Plant Biotechnology Department, National Research Centre (NRC), Cairo, Egypt

    Moemen S. Hanafy, Mohamed A. Matter & M. R. Rady

Authors
  1. Moemen S. Hanafy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mohamed A. Matter
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. R. Rady
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Moemen S. Hanafy .

Editor information

Editors and Affiliations

  1. Biological and Health Sciences Center, Federal University of Maranhao, Sao Luis, Maranhão, Brazil

    Sonia Malik

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Hanafy, M.S., Matter, M.A., Rady, M.R. (2017). Production of Indole Alkaloids in Catharanthus roseus L. Hairy Root Cultures. In: Malik, S. (eds) Production of Plant Derived Natural Compounds through Hairy Root Culture . Springer, Cham. https://doi.org/10.1007/978-3-319-69769-7_5

Download citation

Publish with us

Policies and ethics

Search

Navigation