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Transgenic studies for modulating terpenoid indole alkaloids pathway in Catharanthus roseus: present status and future options

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Abstract

The anti-neoplastic herb Catharanthus roseus (Madagascar periwinkle; Family Apocynaceae), known to harbor >130 bioactive terpenoid indole alkaloids (TIAs), is in global attention of transgenic research for pathway engineering. This medicinal herb has a long folklore history of its usage in the treatment of several health disorders owing to the presence of a variety of secondary metabolites, particularly the alkaloids, phenolics and anthocyanins. Among its various bioactive molecules, C. roseus is most valued for being the exclusive bio-resource of two of the most effective anti-cancerous drugs—vincristine and vinblastine that are indispensible components of several modern day chemotherapeutic regimens. The in-planta yields of these bioactive TIAs are extremely low (<0.0002 %) owing to very rigid developmental, genetical and environmental regulation controls as a part of plant’s own auto-protection strategies against these cytotoxic molecules. Consequently the high cost of production coupled with increasing market demand for these alkaloidal drugs have made TIAs pathway as one of the preferred target for plant metabolic engineering efforts to boost their commercial production. The transgenic approaches so far applied in C. roseus can be grouped into three major lines of investigations. The first line of efforts have been dominated by the genetic transformation studies carried out with wild type Ti or Ri plasmids to measure the influence of their random insertion on TIAs biogenesis. These studies, besides helping the optimization of basic transformation protocols at different levels of cellular differentiation, have largely contributed towards the better resolution and expression of TIAs pathway architecture at the level of associated genes and enzymes. Second line of metabolic engineering works is being centered around the efforts on preparation of genomic libraries and genome mapping to hunt for TIAs pathway genes and associated transcription regulators/factors, followed by their cloning, insertion and hyper-expression to modulate the carbon flux towards desired end products. Modern day transgenic attempts in C. roseus are largely focused on superimposing the concurrent influences of biotic and abiotic elicitation, T-DNA activation and RNAi or virus induced gene silencing approaches for higher TIAs biogenesis. The pace of transgenic research in C. roseus in last two decade has been rapid and demands periodic compilation and reviewing of published literature to provide a handy status up-date of the subject. The present compilation is an effort in this direction and intends to provide a state-of-art account of various transgenic approaches currently being pursued in this high value herb. More than 130 research papers have appeared on various aspects of transgenic cells, tissues and plant production in C. roseus in 30 years. The bulk of these efforts (64.96 %) were made at the level of Agrobacterium rhizogenes-mediated hairy root cultures, followed by 26.80 % in A. tumefaciens-mediated transformed tissues and 8.24 % in cells/tissue cultures subjected to particle bombardment approach. In the present compilation, these studies are further grouped into specific categories wherein over-expression of TIAs pathway specific genes, transcriptional factor regulation, elicitation/stress superimposition, transgenic plant regeneration, metabolites profiling and gene silencing etc. were investigated in different transformed tissue.

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Abbreviations

TIAs:

Terpenoid indole alkaloids

MIAs:

Monoterpenoid indole alkaloids

RNAi:

RNA interference

VIGS:

Virus induced gene silencing

VLB:

Vinblastine

VCR:

Vincristine

ORCA2:

Octadecanoid derivative responsive Catharanthus AP2 domain

ZCTs:

Zinc finger Catharanthus transcription factors

TDC:

Tryptophan decarboxylase

STR:

Strictosidine synthase

DAT:

Deacetyl vindoline 4-O-acetyltransferase

GUS:

3-Glucuronidase

SAAT:

Sonication-assisted Agrobacterium transformation

ORFs:

Open reading frames

T-DNA:

Transfer de-oxy ribonucleic acid

GFP:

Green fluorescent protein

ASα:

Anthranilate synthase alpha unit

MEP:

Methyl-erythritol phosphate pathway

DXP:

1-Deoxy-d-xylulose-5-phosphate

NADPH:

Nicotinamide adenine dinucleotide phosphate (reduced)

SLS:

Secologanin synthase

SGD:

Strictosidine β-d-glucosidase

D4H:

Desacetoxyvindoline 4-hydroxylase

G10H:

Geraniol 10-hydroxylase

DXS:

1-Deoxy-d-xylulose synthase

NMT:

N-Methyl transferase

JERE:

Jasmonate-and elicitor-responsive element

PTGS:

Post-transcriptional gene silencing

TRV:

Tobacco rattle virus

References

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

    Google Scholar 

  • Ayora TT, Chappell J, Lozoya GE, Loyola VVM (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  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 

  • Begum F (2011) Augmented production of vincristine in induced tetraploids of Agrobacterium transformed shooty teratomas of Catharanthus roseus. Med Plant Int J Phyto Relat Ind 3:59–64

    Article  Google Scholar 

  • Begum F, Rao SSSN, Rao K, Devi YP, Giri A, Giri CC (2009) Increased vincristine production from Agrobacterium tumefaciens C58 induced shooty teratomas of Catharanthus roseus G. Don. Nat Prod Lett 23:973–981

    Article  CAS  Google Scholar 

  • Bernonville TD, Clastre M, Besseau S, Oudin A, Burlat V, Glévarec G, Lanoue A, Papon N, Giglioli-Guivarch N, St-Pierre B, Courdavault V (2015) Phytochemical genomics of the Madagascar periwinkle: Unravelling the last twists of the alkaloid engine. Phytochemistry 113:9–23

    Article  CAS  Google Scholar 

  • Bhadra R, Shanks JV (1995) Statistical design of the effect of inoculum conditions on growth of hairy root cultures of Catharanthus roseus. Biol Tech 9:681–686

    CAS  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. Biotech Bioeng 41:581–592

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Binder BYK, Peebles CAM, 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 

  • Borgio J (2009) RNA Interference (RNAi) technology: a promise tool for medicinal plant research. J Med Plants Res 3:1176–1183

    CAS  Google Scholar 

  • Brillanceau MH, David C, Tempé J (1989) Genetic transformation of Catharanthus roseus G. Don by Agrobacterium rhizogenes. Plant Cell Rep 8:63–66

    Article  CAS  PubMed  Google Scholar 

  • Brown S, Clastre M, Courdavault V, O’Connor S (2015) De novo production of the plant-derived alkaloid strictosidine in yeast. PNAS 112:3205–3210

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bulgakov VP (2008) Functions of rol genes in plant secondary metabolism. Biotechnol Adv 26:318–324

    Article  CAS  PubMed  Google Scholar 

  • Burch-Smith TM, Anderson JC, Martin GB, Dinesh-Kumar SP (2004) Applications and advantages of virus-induced gene silencing for gene function studies in plants. Plant J 39:734–746

    Article  CAS  PubMed  Google Scholar 

  • Burlat V, Oudin A, Courtois M, Rideau M, St-Pierre B (2004) Co-expression of three MEP pathway genes and geraniol 10-hydroxylase in internal phloem parenchyma of Catharanthus roseus implicates multicellular translocation of intermediates during the biosynthesis of monoterpene indole alkaloids and isoprenoid-drived primary metabolites. Plant J 38:131–141

    Article  CAS  PubMed  Google Scholar 

  • Busov VB, Meilan R, Pearce DW, Ma C, Rood SB, Strauss SH (2003) Activation tagging of a dominant gibberellin catabolism gene (GA 2-oxidase) from popular that regulates tree stature. Plant Physiol 132:1283–1291

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Canel C, Lopes-Cardoso MI, Whitmer S, Van-Der-Fits L, Pasquali G, Van-Der-Heijden R, Hoge JH, Verpoorte R (1998) Effects of over-expression of strictosidine synthase and tryptophan decarboxylase on alkaloid production by cell cultures of Catharanthus roseus. Planta 205:414–419

    Article  CAS  PubMed  Google Scholar 

  • Chang C, Kwok SF, Bleecker AB, Meyerowitz EM (1993) Arabidopsis ethylene-response gene ETR1: similarity of product to two-component regulators. Science 262:539–544

    Article  CAS  PubMed  Google Scholar 

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

    CAS  Google Scholar 

  • Choi PS, Kim YD, Choi KM, Chung HJ, Choi DW, Liu JR (2004) Plant regeneration from hairy root cultures transformed by infection with A. rhizogenes in Catharanthus roseus. Plant Cell Rep 22:823–831

    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, Ahmad A, Ali M, Lee OK, Kim MY, Kim JH, Yoon DY, Peebles CAM, San KY (2009) Flavonoid glucosides from the hairy roots of Catharanthus roseus. J Nat Prod 72:613–620

    Article  CAS  PubMed  Google Scholar 

  • Ciau-Uitz R, Miranda-Ham ML, Coello-Coello J, Chi B, Pacheco M, Loyola-Vargas VM (1994) Indole alkaloid production by transformed and non-transformed root. In Vitro Cell Dev Biol 30:84–88

    Article  Google Scholar 

  • Collu G, Unverab N, Peltenburg-Loomana AMG, Heijdena RVD, Verpoorte R, Memelink J (2001) Geraniol 10-hydroxylase1, a cytochrome P450 enzyme involved in terpenoid indole alkaloid biosynthesis. FEBS Lett 508:215–220

    Article  CAS  PubMed  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 

  • Courdavault V, Thiersault M, Courtois M, Gantet P, Oudin A, Doireau P, St-Pierre B, Giglioli-Guivarc’h N (2005) CaaX-prenyltransferases are essential for expression of genes involvedin the early stages of monoterpenoid biosynthetic pathway in Catharanthus roseus cells. Plant Mol Biol 57:855–870

    Article  CAS  PubMed  Google Scholar 

  • De Fiore S, Fisher N, Schillberg S (2004) Transient gene expression of recombinant terpenoid indole alkaloid enzymes in Catharanthus roseus leaves. Plant Mol Biol Rep 22:15–22

  • De Luca V, Cutler AJ (1987) Subcellular localization of enzymes involved in indole alkaloid biosynthesis in Catharanthus roseus. Plant Physiol 85:1099–1102

    Article  PubMed  PubMed Central  Google Scholar 

  • Duarte P, Memelink J, Sottomayor M (2010) Fusions with fluorescent proteins for subcellular localization of enzymes involved in plant alkaloid biosynthesis. In: Fett-Netto A (ed) Methods in molecular biology, metabolic engineering of plant secondary pathways. Humana Press, New York, pp 275–290

    Chapter  Google Scholar 

  • Echevarría-Machado I, Muñoz-Sánchez A, Loyola-Vargas VM, Hernández-Sotomayor SMT (2002) Spermine stimulation of phospholipase C from Catharanthus roseus transformed roots. J Plant Physiol 159:1179–1188

    Article  Google Scholar 

  • Echevarría-Machado I, Martínez-Estévez M, Muño-Sánchez JA, Loyola-Vargas VM, Hernández-Sotomayor SMT, Santos-Briones CDL (2007) Membrane-associated phosphoinositides-specific phospholipase C forms from Catharanthus roseus transformed roots. Mol Biotechnol 35:297–309

    Article  PubMed  Google Scholar 

  • Eilert U, De-Luca V, Kurtz WGW, 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 (2007) Catharanthus terpenoid indole alkaloids: biosynthesis and regulation. Phytochem Rev 6:277–305

    Article  CAS  Google Scholar 

  • Facchini PJ (2001) Alkaloid biosynthesis in plants: biochemistry, cell biology, molecular regulation, and metabolic engineering applications. Ann Rev Plant Mol Biol 52:29–66

    Article  CAS  Google Scholar 

  • Facchini PJ, De Luca V (2008) Opium poppy and Madagascar periwinkle: model non-model systems to investigate alkaloid biosynthesis in plants. Plant J 54:763–784

    Article  CAS  PubMed  Google Scholar 

  • Foye WO (1995) Cancer chemotherapeutic agents. American Chemical Society, Washington, pp 349–353

    Google Scholar 

  • Furini A, Koncz C, Salamini F, Bartels D (1997) High level transcription of a member of a repeated gene family confers dehydration tolerance to callus tissue of Craterostigma plantagineum. EMBO J 16:3599–3608

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gamborg OL, Miller RA, Ojima K (1968) Nutrient requirements of suspension cultures of soyabean root cells. Exp Cell Res 50:151–158

    Article  CAS  PubMed  Google Scholar 

  • Gamier F, Carpin S, Label P, Crèche J, Rideau M, Hamdi S (1996a) Effect of cytokinin on alkaloid accumulation in periwinkle callus cultures transformed with a light-inducible ipt gene. Plant Sci 120:47–55

    Article  Google Scholar 

  • Gamier F, Label P, Hallard D, Chénieux JC, Rideau M, Hamdi S (1996b) Transgenic periwinkle tissues overproducing cytokinins do not accumulate enhanced levels of indole alkaloids. Plant Cell Tissue Organ Cult 45:223–230

    Article  Google Scholar 

  • Goddijn OJM, Pennings EJM, van der Helm P, Verpoorte R, Hoge JHC (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. Trans Res 4:315–323

    Article  CAS  Google Scholar 

  • Godoy-Hernández G, Loyola-Vargas VM (1997) Effect of acetylsalicylic acid on secondary metabolism of Catharanthus roseus tumor suspension cultures. Plant Cell Rep 16:287–290

    Article  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Guirimand G, Burlat V, Oudin A, Lanoue A, Pierre BS, Courdavault V (2009) Optimization of the transient transformation of Catharanthus roseus cells by particle bombardment and its application to the subcellular localization of hydroxymethylbutenyl 4-diphosphate synthase and geraniol 10-hydroxylase. Plant Cell Rep 28:1215–1234

    Article  CAS  PubMed  Google Scholar 

  • Guirimand G, Courdavault V, St-Pierre B, Burlat V (2010) Biosynthesis and regulation of alkaloids. In: Pua EC, Davey MR (eds) Plant developmental biology-biotechnological perspective. Springer-Verlag, Heidelberg, pp 139–160

  • Guirimand G, Ginis O, Guihur A, Pierre P, Hericourt F, Oudin A, Lasnoue A, St-Pierre B, Burlat V, Coutdavault V (2011a) The sub-cellular organization of strictosidine biosynthesis in Catharanthus roseus epidermis highlights several trans-tonoplast translocations of intermediate metabolites. FEBS J 278:749–763

    Article  CAS  PubMed  Google Scholar 

  • Guirimand G, Guihur A, Pierre P, Hericourt F, Mahroug S, St-Pierre B, Burlat V, Coutdavault V (2011b) Spatial organization of the vindoline biosynthetic pathway in Catharanthus roseus. J Plant Physiol 168:519–628

    Article  CAS  Google Scholar 

  • Guo XR, Zu YG, Tang ZH (2012) Physiological responses of Catharanthus roseus to different nitrogen forms. Acta Physiol Plant 34:589–598

    Article  CAS  Google Scholar 

  • Hernández-Sotomayor SMT, Santos-Briones CDL, Muñoz-Sánchez JA, Loyola-Vargas VM (1999) Kinetic analysis of phospholipase C from Catharanthus roseus transformed roots using different assays. Plant Physiol 120:1075–1082

    Article  PubMed  PubMed Central  Google Scholar 

  • Hilliou F, Christou P, Leech MJ (1999) Development of an efficient transformation system for Catharanthus roseus cell cultures using particle bombardment. Plant Sci 140:179–188

    Article  CAS  Google Scholar 

  • Hong SB, Hughes EH, Shanks JV, San KY, Gibson SI (2003) Role of the non-mevalonate pathway in indole alkaloid production by Catharanthus roseus hairy roots. Biotechnol Prog 19:1105–1108

    Article  CAS  PubMed  Google Scholar 

  • Hong SB, Peebles CAM, Shanks JV, San KY, Gibson SI (2005) Terpenoid indole alkaloid production by Catharanthus roseus hairy roots induced by Agrobacterium tumefaciens harboring rol ABC genes. Biotechnol Bioeng 93:386–390

    Article  CAS  Google Scholar 

  • Hong SB, Peebles CAM, Shanks JV, San KY, 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 

  • Huang CH, Shanks JV (1992) Effects of initial medium pH on growth and metabolism of Catharanthus roseus hairy root cultures—a study with 31P and 13C NMR spectroscopy. Biotechnol Lett 14:959–964

    Article  Google Scholar 

  • Hughes RH, Shanks JV (2002) Metabolic engineering of plants for alkaloid production. Metab Eng 4:41–48

    Article  CAS  PubMed  Google Scholar 

  • Hughes EH, Hong SB, Shanks JV, San KY, Gibson SI (2002) Characterization of an inducible promoter system in Catharanthus roseus hairy roots. Biotechnol Prog 18:1183–1186

    Article  CAS  PubMed  Google Scholar 

  • Hughes EH, Hong SB, Gibson SI, Shanks JV, San KY (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, Miranda-Ham ML (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 30:81–83

    Article  Google Scholar 

  • Islas-Flores II, Zúñiga-Aguilar JJ, Rodríguez-Zapata LC, Carrillo-Pech M, Baízabal-Aguirre VM, Minero-García Y, Hernández-Sotomayor SMT (2004) MAP kinase-like activity in transformed Catharanthus roseus hairy roots varies with culture conditions such as temperature and hypo-osmotic shock. Plant Physiol Biochem 42:65–72

    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 

  • Johnson S, Armstrong I, James G, Marvin G, Burnett JP (1963) The vinca alkaloids: a new class of oncolytic agents. Lilly laboratories for Research and Lilly Laboratories for Clinical Research, Indianapolis, pp 1390–1427

    Google Scholar 

  • Jun XM, Fang DJ (2007) Enhancing terpenoid indole alkaloid production by inducible expression of mammalian Bax in Catharanthus roseus cells. Sci China Ser C Life Sci 50:234–241

    Article  CAS  Google Scholar 

  • Jung KH, Kwak SS, Kim SW, Lee H, Choi CY, Liu JR (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 (1994) Development of two stage culture process by optimization of inorganic salts for improving catharanthine production in hairy root cultures of Catharanthus roseus. J Ferment Bioeng 77:57–61

    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 for indole alkaloid production. Plant Cell Rep 15:51–54

    Article  CAS  PubMed  Google Scholar 

  • Kakimoto T (1996) CKI1, a histidine kinase homolog implicated in cytokinin signal transduction. Science 274:982–985

    Article  CAS  PubMed  Google Scholar 

  • Krishnan A, Mahadevan C, Mani T, Sakuntala M (2015) Virus-induced gene silencing (VIGS) for elucidation of pathogen defense role of serine/threonine protein kinase in the non-model plant Piper colubrinum Link. Plant Cell Tiss Organ Cult 122:269–283

    Article  CAS  Google Scholar 

  • Kumar S, Dutta A, Sinha AK, Sen J (2007) Cloning, characterization and localization of a novel basic peroxidase gene from Catharanthus roseus. FEBS J 274:1290–1303

    Article  CAS  PubMed  Google Scholar 

  • Kumar S, Jaggi M, Taneja J, Sinha AK (2011) Cloning and characterization of two new Class III peroxidase genes from Catharanthus roseus. Plant Physiol Biochem 49:404–412

    Article  CAS  PubMed  Google Scholar 

  • Laflamme P, St-Pierre B, De Luca V (2001) Molecular and biochemical analysis of a Madagascar periwinkle root-specific minovincinine-19-hydroxy-O-acetyltransferase. Plant Physiol 125:189–198

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li M, Peebles CAM, Shanks JV, San KY (2011) Effect of sodium m 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 

  • Liscombe DK, O’Connor SE (2011) A virus induced gene silencing approach to understand alkaloid metabolism in Catharanthus roseus. Phytochemistry 72:1969–1977

    Article  CAS  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 10:3260–3268

    Article  CAS  Google Scholar 

  • Loyola-Vargas VM, Galaz-Avalos RM, Rodríguez-Ku JR (2007) Catharanthus biosynthetic enzymes: the road ahead. Phytochem Rev 6:307–339

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Mahroug S, Burlat V, St-Pierre B (2007) Cellular and sub-cellular organization of the monoterpenoid indole alkaloid pathway in Catharanthus roseus. Phytochem Revolut 6:363–381

    Article  CAS  Google Scholar 

  • Mathews H, Clendennen SK, Caldwell CG, Liu XL, Connors K, Matheis N, Schuster DK, Menasco DJ, Wagoner W, Lightner J, Wagner DR (2003) Activation tagging in tomato identifies a transcriptional regulator of anthocyanin biosynthesis, modification, and transport. Plant Cell 15:1689–1703

    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 

  • Memelink J, Verpoorte R, Kijne JW (2001) ORCAnisation of jasmonate responsive gene expression in alkaloid metabolism. Trends Plant Sci 6:212–219

    Article  CAS  PubMed  Google Scholar 

  • Montieal G, Bretona C, Thiersaulta M, Burlata V, Allemanda CJ, Ganteta P (2007) Transcription factor Agamous-like 12 from Arabidopsis promotes tissue-like organization and alkaloid biosynthesis in Catharanthus roseus suspension cells. Metab Eng 9:125–132

    Article  CAS  Google Scholar 

  • Moreno-Valenzuela OA, Galaz-Avalos RM, Minero-García Y, Loyola-Vargas VM (1998) Effect of differentiation on the regulation of indole alkaloid production in Catharanthus roseus hairy roots. Plant Cell Rep 18:99–104

    Article  CAS  Google Scholar 

  • Moreno-Valenzuela O, Coello-Coello J, Loyola-Vargas VM, Vázquez-Flota F (1999) Nutrient consumption and alkaloid accumulation in a hairy root line of Catharanthus roseus. Biotechnol Lett 21:1017–1021

    Article  CAS  Google Scholar 

  • Moreno-Valenzuela OA, Minero-García Y, Brito-Argáez L, Carbajal-Mora E, Echeverría O, Vázquez-Nin G, Loyola-Vargas VM (2003a) Immunocytolocalization of tryptophan decarboxylase in Catharanthus roseus hairy roots. Mol Biotechnol 23:11–18

    Article  CAS  PubMed  Google Scholar 

  • Moreno-Valenzuela OA, Minero-García Y, Chan W, Mayer-Geraldo E, Carbajal E, Loyola-Vargas VM (2003b) 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 Catharanthus 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 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 53:262–265

    Article  CAS  PubMed  Google Scholar 

  • Murata J, De Luca V (2005) Localization of tabersonine 16-hydroxylase and 16-OH-tabersonine-16-O-methyltransferase to leaf epidermal cells defines them as a major site of precursor biosynthesis in the vindoline pathway in Catharanthus roseus. Plant J 44:581–594

    Article  CAS  PubMed  Google Scholar 

  • Murata J, Bienzle D, Brandle JE, Sensen CW, De Luca V (2006) Expressed sequence tags from Madagascar periwinkle (Catharanthus roseus). FEBS Lett 580:4501–4507

    Article  CAS  PubMed  Google Scholar 

  • Murata J, Roepke J, Gordon H, De Luca V (2008) The leaf epidermome of Catharanthus roseus reveals its biochemical specialization. Plant Cell J 20:524–542

    Article  CAS  Google Scholar 

  • Neff MM, Nguyen SM, Malancharuvil EJ, Fujioka S, Noguchi T, Seto H et al (1999) BAS1: a gene regulating brassinosteroid levels and light responsiveness in Arabidopsis. PNAS USA 96(15):316–323

    Google Scholar 

  • Neuss N, Neuss MN (1990) The therapeutic use of bisindole alkaloids from Catharanthus. In: Brossi A, Suffness M (eds) The alkaloids, vol 37. Academic press, San Diego, pp 228–240

    Google Scholar 

  • Nuutila AM, 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’Connor SE, Maresh JM (2006) Chemistry and biology of terpene indole alkaloid biosynthesis. Nat Prod Rep 23:532–547

    Article  PubMed  CAS  Google Scholar 

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

    Article  Google Scholar 

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

    Article  Google Scholar 

  • Palni LMS (1984) Cytokinin accumulation in the culture medium of Vinca rosea L. crown-gall tissue: a time-course study. Aust J Plant Physiol 11:129–136

    Article  CAS  Google Scholar 

  • Palni LMS, Horgan R (1983) Cytokinins in transfer RNA of normal and crown-gall tissue of Vinca rosea. Planta 159:178–181

    Article  CAS  PubMed  Google Scholar 

  • Palni LMS, Horgan R, Darrall NM, Stuchbury T, Wareing PF (1983) Cytokinin biosynthesis in crown gall tissue of Vinca rosea: significance of nucleotide. Planta 159:50–59

    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 

  • Pan Q, Rianika N, Mustafa Tang K, Choi YH, Verpoorte R (2015) Monoterpenoid indole alkaloids biosynthesis and its regulation in Catharanthus roseus: a literature review from genes to metabolites. Phytochem Rev. doi:10.1007/s111c1-015-9406-4

    Google Scholar 

  • Papon N, Vansiri A, Gantet P, Chenieux JC, Rideau M, Creche J (2004) Histidine-containing phosphor-transfer domain extinction by RNA interference turns off a cytokinin signalling circuitry in Catharanthus roseus suspension cells. FEBS Lett 558:85–88

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Pauw B, Hilliou FAO, Martin VS, Chatel G, Wolf CJFD, Champion A, Pré M, Duijn BV, Kijne JW, Fits LVD, Memelink J (2004) Zinc finger proteins act as transcriptional repressors of alkaloid biosynthesis genes in Catharanthus roseus. J Biol Chem 279:52940–52948

    Article  CAS  PubMed  Google Scholar 

  • Peebles CAM, Hong SB, Gibson SI, Shanks JV, San KY (2005) Transient effects of over-expressing anthranilate synthase α and β subunits in Catharanthus roseus hairy roots. Biotechnol Prog 21:1572–1576

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Peebles CAM, Gibson SI, Shanks JV, San KY (2007b) Long-term maintenance of a transgenic Catharanthus roseus hairy root line. Biotech Prog 23:1517–1518

    Article  CAS  Google Scholar 

  • Peebles CAM, Hughes EH, Shanks JV, San KY (2009a) 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 CAM, Shanks JV, San KY (2009b) The role of the octadecanoid pathway in the production of terpenoid indole alkaloids in Catharanthus roseus hairy roots under normal and UV-B stress conditions. Biotechnol Bioeng 103:1248–1254

    Article  CAS  PubMed  Google Scholar 

  • Peebles CAM, 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 13:234–240

    Article  CAS  PubMed  Google Scholar 

  • Piña-Chable ML, Santos-Briones C, Muñoz-Sánchez JA, Echevarría MI, Hernández-Sotomayor SM (1998) Effect of different inhibitors on phospholipase C activity in Catharanthus roseus transformed roots. Prostaglandin Other Lipid Mediat 56:19–31

    Article  Google Scholar 

  • Pina-Chable ML, Hernandez-Sotomayor SM (2001) Phospholipase C activity from Catharanthus roseus transformed roots: aluminium effect. Prostaglandin Other Lipid Mediat 65:45–56

  • Qu Y, Easson MLAE, Froese J, Simionescu R, Hudlicky T, De Luca V (2015) Completion of the seven-step pathway from tabersonine to the anticancer drug precursor vindoline and its assembly in yeast. PNAS USA 112:6224–6229

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rai A, Smita SS, Singh AK, Shanker K, Nagegowda DA (2013) Heteromeric and homomeric geranyl diphosphate synthases from Catharanthus roseus and their role in monoterpene indole alkaloid biosynthesis. Mol Plant 6:1531–1549

    Article  CAS  PubMed  Google Scholar 

  • Rijhwani SK, Shanks JV (1998a) 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 

  • Rijhwani SK, Shanks JV (1998b) Effect of subculture cycle on growth and indole alkaloid production by Catharanthus roseus hairy root cultures. Enzyme Microb Technol 22:606–611

    Article  CAS  Google Scholar 

  • Rischer H, Oresic M, Seppanen-Laakso T, Katajamaa M, Lammertyn F, Ardiles-Diaz W, Montagu MCE, Inzé D, Oksman-Caldentey KM, Goossens A (2006) Gene-to-metabolite networks for terpenoid indole alkaloid biosynthesis in Catharanthus roseus cells. PNAS USA 103:5614–5619

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rizvi N, Weaver J, Cornejo M, Stein K, Cram EJ, Lee-Parson CWT (2015) An efficient transformation method for estrogen-inducible transgene expression in Catharanthus roseus hairy roots. Plant Cell Tissue Organ Cult. doi:10.1007/s11240-014-0614-1

    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 

  • Rodríguez-Zapata LC, Hernández-Sotomayor SMT (1998) Evidence of protein-tyrosine kinase activity in Catharanthus roseus roots transformed by Agrobacterium rhizogenes. Planta 204:70–77

    Article  PubMed  Google Scholar 

  • Roepke J, Salim V, Wu M, Thamm AMK, Murata J, Ploss K, Boland W, De Luca V (2010) Vinca drug components accumulate exclusively in leaf exudates of Madagascar periwinkle. PNAS USA 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 41:278–285

    Article  CAS  PubMed  Google Scholar 

  • Ruiz-May E, De-la-Peña C, Galaz-Ávalos RM, Lei Z, Watson BS, Sumner LW, Loyola-Vargas VM (2011) Methyl jasmonate induces ATP biosynthesis deficiency and accumulation of proteins related to secondary metabolism in Catharanthus roseus (L.) G. hairy roots. Plant Cell Physiol 52:1401–1421

    Article  CAS  PubMed  Google Scholar 

  • Runguphan W, Maresh JJ, O’Connor SE (2009) Silencing of tryptamine biosynthesis for production of nonnatural alkaloids in plant culture. PNAS USA 106:13673–13678

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Salim V, Yu F, Altarejos J, 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 

  • Santos-Briones CDL, Muñoz-Sánchez JA, Vera JC, Loyola VM (1997) Phosphatidylinositol 4, 5-bisphosphate—phospholipase C activity during the growing phase of Catharanthus roseus transformed roots. J Biochem 97:69–78

    Google Scholar 

  • Schneuwly S, Klemenz R, Gehring WJ (1987) Redesigning the body plan of Drosophila by ectopic expression of the homoeotic gene Antennapedia. Nature 325:816–818

    Article  CAS  PubMed  Google Scholar 

  • Sevon N, Oksman-Caldentey K (2002) Agrobacterium rhizogenes-mediated transformation: root culture as a source of alkaloids. Plant Med 68:859–868

    Article  CAS  Google Scholar 

  • Shanks JV, Morgan J (1999) Plant hairy root culture. Curr Opin Biotechnol 10:151–155

  • Shukla A, Shasany AK, Verma RK, Gupta MM, Mathur AK, Khanuja SPS (2010) Influence of cellular differentiation and elicitation on intermediate and late steps of terpenoid indole alkaloid biosynthesis in Catharanthus roseus. Protoplasma 242:35–47

    Article  CAS  PubMed  Google Scholar 

  • Sim SS, 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 783:229–234

    Google Scholar 

  • Sottomayor M, Ros Barceló A (2003) Peroxidase from Catharanthus roseus (L.) G. Don and the biosynthesis of alpha-3′,4′-anhydrovinblastine: a specific role for a multifunctional enzyme. Protoplasma 222:97–105

    Article  CAS  PubMed  Google Scholar 

  • Sottomayor M, De Pinto MC, Salema R, DiCosmo F, Pedreno MA, Ros Barcelo A (1996) The vacuolar localization of a basic peroxidase isoenzyme responsible for the synthesis of a α-3′,4′-anhydrovinblastine in Catharanthus roseus (L.) G. Don leaves. Plant Cell Environ 19:761–767

    Article  CAS  Google Scholar 

  • Sottomayor M, Lopez-Serrano M, DiCosmo F, Ros-Barcelo A (1998) Purification and characterization of α-3′,4′-anhydrovinblastine synthase (peroxidase-like) from Catharanthus roseus (L.) G. Don. FEBS Lett 428:299–303

    Article  CAS  PubMed  Google Scholar 

  • Srivastava T, Das S, Sopory SK, Srivastava PS (2009) A reliable protocol for transformation of Catharanthus roseus through Agrobacterium tumefaciens. Physiol Mol Biol Plant 15:93–98

    Article  CAS  Google Scholar 

  • Stockigt J, Panjikar S (2007) Structural biology in plant natural product biosynthesis-architecture of enzymes from monoterpene indole and tropane alkaloid biosynthesis. Nat Prod Rep 24:1382–1400

    Article  PubMed  CAS  Google Scholar 

  • St-Pierre B, De Luca V (1995) A cytochrome P-450 monooxygenase catalyzes the first step in the conversion of tabersonine to vindoline in Catharanthus roseus. Plant Physiol 109:131–139

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • St-Pierre B, Vazquez-Flota FA, De Luca V (1999) Multicellular compartmentation of Catharanthus roseus alkaloid biosynthesis predicts intercellular translocation of a pathway intermediate. Plant Cell 11:887–900

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sung YC, Lin CP, Chen JC (2014) Optimization of virus-induced gene silencing in Catharanthus roseus. Plant Pathol 63:1159–1167

    Article  CAS  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 

  • Taha HS, Abo-Aba SEM, El-Hamshary OIM, Abdel-Azeim NS, Nazif NM, El-Bahr MK, El-Nasr MMS (2008) In vitro studies on Egyptian Catharanthus roseus (L.) G. Don: III. Effects of extra tryptophan decarboxylase and strictosidine synthase genes copies in indole alkaloid production. Res J Cel Mol Biol 2:18–23

    CAS  Google Scholar 

  • Taneja J, Jaggi M, Wankhede DP, Sinha AK (2010) Effect of loss of T-DNA genes on MIA biosynthetic pathway gene regulation and alkaloid accumulation in Catharanthus roseus hairy roots. Plant Cell Rep 29:1119–1129

    Article  CAS  PubMed  Google Scholar 

  • Tang KX, Liu DH, Wang YL, Cui LJ, Ren WW, Sun XF (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 AK, Sinha AK (2013) Yield enhancement strategies for enhancement of indole alkaloids in hairy root cultures of Catharanthus roseus. Int J Chem Eng Appl 4:153–156

    CAS  Google Scholar 

  • Tikhomiroff C, Allais S, Klvana M, Hisiger S, Jolicoeur M (2009) Continuous selective extraction of secondary metabolites from Catharanthus roseus hairy roots with silicon oil in a two-liquid-phase bioreactor. Biotechnol Prog 18:1003–1009

    Article  CAS  Google Scholar 

  • Toivonen L, Balsevich J, Kurz WGW (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 (1990) Indole alkaloid production by hairy root cultures of Catharanthus roseus: growth kinetics and fermentation. Biotechnol Lett 12:519–524

    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 37:673–680

  • 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 

  • Trémouillaux-Guiller J, Kodja H, Chénieux JC (1994) Single-cell cloning of a crown gall from protoplasts regenerated in hormone-free medium, Establishment of pure transformed cell-lines of Catharanthus roseus. Plant Cell Tissue Org Cult 37:25–30

    Article  Google Scholar 

  • Van der Fits L, Memelink J (1997) Comparison of the activities of CaMV 35S and FMV 34S promoter derivatives in Catharanthus roseus cells transiently and stably transformed by particle bombardment. Plant Mol Biol 33:943–946

    Article  PubMed  Google Scholar 

  • Van der Fits L, Memelink J (2000) ORCA3, a jasmonate-responsive transcriptional regulator of plant primary and secondary metabolism. Science 289:295–297

    Article  PubMed  Google Scholar 

  • Van der Fits L, Hilliou F, Memelink J (2001) T-DNA activation tagging as a tool to isolate regulators of a metabolic pathway from a genetically non-tractable plant species. Trans Res 10:513–521

    Article  Google Scholar 

  • Van der Heijden R, Jabos DJ, Snoeijer W, Hallard D, Verpoorte R (2004) The Catharanthus alkaloids: pharmacognosy and biotechnology. Curr Med Chem 11:1241–1253

    Article  Google Scholar 

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

    Article  Google Scholar 

  • Verma P, Mathur AK (2011a) Direct shoot bud organogenesis and plant regeneration from leaf explants in Catharanthus roseus. Plant Cell Tissue Organ Cult 106:401–408

    Article  CAS  Google Scholar 

  • Verma P, Mathur AK (2011b) Agrobacterium tumefaciens-mediated transgenic plant production via direct shoot bud organogenesis from pre-plasmolyzed leaf explants of Catharanthus roseus. Biotechnol Lett 33:1053–1060

    Article  CAS  PubMed  Google Scholar 

  • Verma P, Mathur AK, Srivastava A, Mathur A (2012a) Emerging trends in research on spatial and temporal organization of terpenoid indole alkaloids pathway in Catharanthus roseus: a literature up-date. Protoplasma 249:255–268

    Article  CAS  PubMed  Google Scholar 

  • Verma P, Mathur AK, Shanker K (2012b) 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 

  • Verma P, Mathur AK, Shankar K (2012c) Increased availability of tryptophan in 5-methyltryptophan tolerant shoots of Catharanthus roseus and their post-harvest in vivo elicitation induces enhanced vindoline production. Appl Biochem Biotechnol 168:568–579

    Article  CAS  PubMed  Google Scholar 

  • Verma P, Sharma A, Khan SA, Mathur AK, Shanker K (2014) Morpho-genetic and chemical stability of long term maintained Agrobacterium mediated transgenic Catharanthus roseus plants. Nat Prod Res 29:315–320

    Article  PubMed  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, Alfermann AW (eds) (2000) Metabolic engineering of plant secondary metabolism. Kluwer Academic Publishers, Dordrecht

  • Verpoorte R, van der Heijden R, Moreno PRH (1997) Biosynthesis of terpenoid indole alkaloids in Catharanthus roseus cells. In: Cordell GA (ed) The alkaloids, vol 49. Academic Press, San Diego, p 221

    Google Scholar 

  • Verpoorte R, Contin A, Memelink J (2002) Biotechnology for the production of plant secondary metabolites. Phytochem Rev 1:13–25

    Article  CAS  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 29:887–894

    Article  CAS  PubMed  Google Scholar 

  • Wang Q, Xing S, Pan Q, Yuan F, Zhao J, Tian Y, Chen Y, Wang G, Tang K (2012) Development of efficient Catharanthus roseus regeneration and transformation system using Agrobacterium tumefaciens and hypocotyls as explants. BMC Biotechol 12:34–46

    Article  CAS  Google Scholar 

  • Weaver J, Goklany S, Rizvi N, Cram EJ, Lee-Parson CWT (2014) Optimizing the transient fast agro-mediated seedling transformation (FAST) method in Catharanthus roseus seedlings. Plant Cell Rep 33:89–97

    Article  CAS  PubMed  Google Scholar 

  • Weigel D, Ahn JH, Blazquez MA, Borevitz JO, Christensen SK, Fankhauser C, Ferrandiz C, Kardailsky I, Malancharuvil EJ, Neff MM, Nguyen JT, Sato S, Wang Z-Y, Xia Y, Dixon RA, Harrison MJ, Lamb CJ, Yanofsky MF, Chory J (2000) Activation tagging in Arabidopsis. Plant Physiol 122:1003–1014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Whitmer S, Canel C, Hallard D, Gonçalves C, Verpoorte R (1998) Influence of precursor availability on alkaloid accumulation by transgenic cell line of Catharanthus roseus. Plant Physiol 116:853–857

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Yang Z, Patra B, Li R, Pattanaik S, Yuan L (2013) Promoter analysis reveals cis-regulatory motifs associated with the expression of the WRKY transcription factor CrWRKY1 in Catharanthus roseus. Planta 238:1039–1049

    Article  CAS  PubMed  Google Scholar 

  • Zarate R, Verpoorte R (2007) Strategies for the genetic modification of the medicinal plant Catharanthus roseus (L.) G. Don. Phytochem Rev 6:475–491

    Article  CAS  Google Scholar 

  • Zarate R, Memelink J, van Der Heijden R, Verpoorte R (1999) Genetic transformation via partical bombardment of Catharanthus roseus plants through adventitious organogenesis of buds. Biotechnol Lett 21:997–1002

    Article  CAS  Google Scholar 

  • Zargar M, Farahani F, Nabavi T (2010) Hairy roots production of transgenic Catharanthus roseus L. plants with Agrobacterium rhizogenes under in vitro conditions. J Med Plant Res 4:2199–2203

    CAS  Google Scholar 

  • Zhang H, Hedhili S, Montiel G, Zhang Y, Chatel G, Pre´ M, Gantet P, Memelink J (2011) The basic helix–loop–helix transcription factor CrMYC2 controls the jasmonate-responsive expression of the ORCA genes that regulate alkaloid biosynthesis in Catharanthus roseus. Plant J 67:61–71

    Article  CAS  PubMed  Google Scholar 

  • Zhou ML, Zhu XM, Shao JR, Wu YM, Tang YX (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 ML, Hou HL, Zhu XM, Shao JR, Wu YM, Tang YX (2011) Soybean transcription factor GmMYBZ2 represses catharanthine biosynthesis in hairy roots of Catharanthus roseus. Appl Microbiol Biotechnol 4:1095–1105

    Article  CAS  Google Scholar 

  • Zhou ML, Zhu XM, Shao JR, Wu YM, Tang YX (2012) An protocol for genetic transformation of Catharanthus roseus by Agrobacterium rhizogenes A4. Appl Biochem Biotechnol 166:1674–1684

    Article  CAS  PubMed  Google Scholar 

  • Zhou C, Zhang J, Zhao SJ, Hu ZB (2014) An active Catharanthus roseus desacetoxyvindoline-4-hydroxylase-like gene and its transcriptional regulatory profile. Bot Stud 55:29

    Article  CAS  Google Scholar 

  • Zhu J, Wang M, Wen W, Yu R (2015) Biosynthesis and regulation of terpenoid indole alkaloids in Catharanthus roseus. Pharmacogn Rev 9:24–48

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

The financial grant given by CSIR and DST-FAST TRACK SERC/LS-261/2012 has been highly acknowledged.

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  1. Department of Plant Biotechnology, Central Institute of Medicinal and Aromatic Plants (CIMAP), Council of Scientific and Industrial Research (CSIR), PO CIMAP, Kukrail Picnic Spot Road, Lucknow, 226015, India

    Priyanka Verma, Ajay Kumar Mathur, Shamshad Ahmad Khan, Neha Verma & Abhishek Sharma

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  1. Priyanka Verma
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Verma, P., Mathur, A.K., Khan, S.A. et al. Transgenic studies for modulating terpenoid indole alkaloids pathway in Catharanthus roseus: present status and future options. Phytochem Rev 16, 19–54 (2017). https://doi.org/10.1007/s11101-015-9447-8

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