Biosynthetic pathway of terpenoid indole alkaloids in Catharanthus roseus

Xiaoxuan Zhu , Xinyi Zeng , Chao Sun , Shilin Chen

Front. Med. ›› 2014, Vol. 8 ›› Issue (3) : 285 -293.

PDF (238KB)
Front. Med. ›› 2014, Vol. 8 ›› Issue (3) : 285 -293. DOI: 10.1007/s11684-014-0350-2
REVIEW
REVIEW

Biosynthetic pathway of terpenoid indole alkaloids in Catharanthus roseus

Author information +
History +
PDF (238KB)

Abstract

Catharanthus roseus is one of the most extensively investigated medicinal plants, which can produce more than 130 alkaloids, including the powerful antitumor drugs vinblastine and vincristine. Here we review the recent advances in the biosynthetic pathway of terpenoid indole alkaloids (TIAs) in C. roseus, and the identification and characterization of the corresponding enzymes involved in this pathway. Strictosidine is the central intermediate in the biosynthesis of different TIAs, which is formed by the condensation of secologanin and tryptamine. Secologanin is derived from terpenoid (isoprenoid) biosynthetic pathway, while tryptamine is derived from indole biosynthetic pathway. Then various specific end products are produced by different routes during downstream process. Although many genes and corresponding enzymes have been characterized in this pathway, our knowledge on the whole TIA biosynthetic pathway still remains largely unknown up to date. Full elucidation of TIA biosynthetic pathway is an important prerequisite to understand the regulation of the TIA biosynthesis in the medicinal plant and to produce valuable TIAs by synthetic biological technology.

Keywords

Catharanthus roseus / terpenoidindole alkaloids / biosynthetic pathway / vinblastine / vincristine

Cite this article

Download citation ▾
Xiaoxuan Zhu, Xinyi Zeng, Chao Sun, Shilin Chen. Biosynthetic pathway of terpenoid indole alkaloids in Catharanthus roseus. Front. Med., 2014, 8(3): 285-293 DOI:10.1007/s11684-014-0350-2

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Oudin A, Courtois M, Rideau M, Clastre M. The iridoid pathway in Catharanthus roseus alkaloid biosynthesis. Phytochem Rev2007; 6(2–3): 259–276

[2]

Facchini PJ, De Luca V. Opium poppy and Madagascar periwinkle: model non-model systems to investigate alkaloid biosynthesis in plants. Plant J2008; 54(4): 763–784

[3]

El-Sayed M, Verpoorte R. Catharanthus terpenoid indole alkaloids: biosynthesis and regulation. Phytochem Rev2007; 6(2–3): 277–305

[4]

van Der Heijden R, Jacobs DI, Snoeijer W, Hallard D, Verpoorte R. The Catharanthus alkaloids: pharmacognosy and biotechnology. Curr Med Chem2004; 11(5): 607–628

[5]

van Tellingen O, Sips JH, Beijnen JH, Bult A, Nooijen WJ. Pharmacology, bio-analysis and pharmacokinetics of the vinca alkaloids and semi-synthetic derivatives. Anticancer Res1992; 12(5): 1699–1715

[6]

Zhao L, Sander GW, Shanks JV. Perspectives of the metabolic engineering of terpenoid indole alkaloids in Catharanthus roseus hairy roots. Adv Biochem Eng Biotechnol2013; 134: 23–54

[7]

Contin A, van der Heijden R, Lefeber AW, Verpoorte R. The iridoid glucoside secologanin is derived from the novel triose phosphate/pyruvate pathway in a Catharanthus roseus cell culture. FEBS Lett1998; 434(3): 413–416

[8]

Courdavault V, Burlat V, St-Pierre B, Giglioli-Guivarc’h N. Characterisation of CaaX-prenyltransferases in Catharanthus roseus: relationships with the expression of genes involved in the early stages of monoterpenoid biosynthetic pathway. Plant Sci2005; 168(4): 1097–1107

[9]

Chahed K, Oudin A, Guivarc’h N, Hamdi S, Chénieux JC, Rideau M, Clastre M. 1-Deoxy-D-xylulose 5-phosphate synthase from periwinkle: cDNA identification and induced gene expression in terpenoid indole alkaloid-producing cells. Plant Physiol Biochem2000; 38(7): 559–566

[10]

Cunningham FX Jr, Lafond TP, Gantt E. Evidence of a role for LytB in the nonmevalonate pathway of isoprenoid biosynthesis. J Bacteriol2000; 182(20): 5841–5848

[11]

Newman JD, Chappell J. Isoprenoid biosynthesis in plants: carbon partitioning within the cytoplasmic pathway. Crit Rev Biochem Mol Biol1999; 34(2): 95–106

[12]

Lange BM, Croteau R. Isopentenyl diphosphate biosynthesis via a mevalonate-independent pathway: isopentenyl monophosphate kinase catalyzes the terminal enzymatic step. Proc Natl Acad Sci USA1999; 96(24): 13714–13719

[13]

Van der Heijden R, Verpoorte R, Duine J. Biosynthesis of 3S-hydroxy-3-methylglutaryl-coenzyme A in Catharanthus roseus: acetoacetyl-CoA thiolase and HMG-CoA synthase show similar chromatographic behaviour. Plant Physiol Biochem1994; 32(6): 807–812

[14]

Maldonado-Mendoza IE, Burnett RJ, Nessler CL. Nucleotide sequence of a cDNA encoding 3-hydroxy-3-methylglutaryl coenzyme A reductase from Catharanthus roseus. Plant Physiol1992; 100(3): 1613–1614

[15]

Schulte AE, van der Heijden R, Verpoorte R. Purification and characterization of mevalonate kinase from suspension-cultured cells of Catharanthus roseus (L.) G. Don. Arch Biochem Biophys2000; 378(2): 287–298

[16]

Schulte AE, Llamas Durán EM, van der Heijden R, Verpoorte R. Mevalonate kinase activity in Catharanthus roseus plants and suspension cultured cells. Plant Sci2000; 150(1): 59–69

[17]

Schulte AE, van der Heijden R, Verpoorte R. Purification and characterization of phosphomevalonate kinase from Catharanthus roseus. Phytochemistry1999; 52(6): 975–983

[18]

Ramos-Valdivia AC, van der Heijden R, Verpoorte R. Isopentenyl diphosphate isomerase and prenyltransferase activities in rubiaceous and apocynaceous cultures. Phytochemistry1998; 48(6): 961–969

[19]

Simkin AJ, Guirimand G, Papon N, Courdavault V, Thabet I, Ginis O, Bouzid S, Giglioli-Guivarc’h N, Clastre M. Peroxisomal localisation of the final steps of the mevalonic acid pathway in planta. Planta2011; 234(5): 903–914

[20]

Guirimand G, Guihur A, Phillips MA, Oudin A, Glévarec G, Melin C, Papon N, Clastre M, St-Pierre B, Rodríguez-Concepción M, Burlat V, Courdavault V. A single gene encodes isopentenyl diphosphate isomerase isoforms targeted to plastids, mitochondria and peroxisomes in Catharanthus roseus. Plant Mol Biol2012; 79(4-5): 443–459

[21]

Han M, Heppel SC, Su T, Bogs J, Zu Y, An Z, Rausch T. Enzyme inhibitor studies reveal complex control of methyl-D-erythritol 4-phosphate (MEP) pathway enzyme expression in Catharanthus roseus. PLoS ONE2013; 8(5): e62467

[22]

Veau B, Courtois M, Oudin A, Chénieux JC, Rideau M, Clastre M. Cloning and expression of cDNAs encoding two enzymes of the MEP pathway in Catharanthus roseus. Biochimica et Biophysica Acta (BBA)—. Gene Structure and Expression2000; 1517(1): 159–163

[23]

Ginis O, Courdavault V, Melin C, Lanoue A, Giglioli-Guivarc’h N, St-Pierre B, Courtois M, Oudin A. Molecular cloning and functional characterization of Catharanthus roseus hydroxymethylbutenyl 4-diphosphate synthase gene promoter from the methyl erythritol phosphate pathway. Mol Biol Rep2012; 39(5): 5433–5447

[24]

Meijer AH, Lopes Cardoso MI, Voskuilen JT, de Waal A, Verpoorte R, Hoge JHC. Isolation and characterization of a cDNA clone from Catharanthus roseus encoding NADPH:cytochrome P-450 reductase, an enzyme essential for reactions catalysed by cytochrome P-450 mono-oxygenases in plants. Plant J1993; 4(1): 47–60

[25]

Simkin AJ, Miettinen K, Claudel P, Burlat V, Guirimand G, Courdavault V, Papon N, Meyer S, Godet S, St-Pierre B, Giglioli-Guivarc’h N, Fischer MJ, Memelink J, Clastre M. Characterization of the plastidial geraniol synthase from Madagascar periwinkle which initiates the monoterpenoid branch of the alkaloid pathway in internal phloem associated parenchyma. Phytochemistry2013; 85: 36–43

[26]

Collu G, Unver N, Peltenburg-Looman AM, van der Heijden R, Verpoorte R, Memelink J. Geraniol 10-hydroxylase, a cytochrome P450 enzyme involved in terpenoid indole alkaloid biosynthesis. FEBS Lett2001; 508(2): 215–220

[27]

Geu-Flores F, Sherden NH, Courdavault V, Burlat V, Glenn WS, Wu C, Nims E, Cui Y, O’Connor SE. An alternative route to cyclic terpenes by reductive cyclization in iridoid biosynthesis. Nature2012; 492(7427): 138–142

[28]

Salim V, Wiens B, Masada-Atsumi S, Yu F, De Luca V. 7-deoxyloganetic acid synthase catalyzes a key 3 step oxidation to form 7-deoxyloganetic acid in Catharanthus roseus iridoid biosynthesis. Phytochemistry2014; 101: 23–31

[29]

Asada K, Salim V, Masada-Atsumi S, Edmunds E, Nagatoshi M, Terasaka K, Mizukami H, De Luca V. A 7-deoxyloganetic acid glucosyltransferase contributes a key step in secologanin biosynthesis in Madagascar periwinkle. Plant Cell2013; 25(10): 4123–4134

[30]

Salim V, Yu F, Altarejos J, De Luca V. Virus-induced gene silencing identifies Catharanthus roseus 7-deoxyloganic acid-7-hydroxylase, a step in iridoid and monoterpene indole alkaloid biosynthesis. Plant J2013; 76(5): 754–765

[31]

Murata J, Roepke J, Gordon H, De Luca V. The leaf epidermome of Catharanthus roseus reveals its biochemical specialization. Plant Cell2008; 20(3): 524–542

[32]

Vetter HP, Mangold U, Schröder G, Marner FJ, Werck-Reichhart D, Schröder J. Molecular analysis and heterologous expression of an inducible cytochrome P-450 protein from periwinkle (Catharanthus roseus L.). Plant Physiol1992; 100(2): 998–1007

[33]

Irmler S, Schröder G, St-Pierre B, Crouch NP, Hotze M, Schmidt J, Strack D, Matern U, Schröder J. Indole alkaloid biosynthesis in Catharanthus roseus: new enzyme activities and identification of cytochrome P450 CYP72A1 as secologanin synthase. Plant J2000; 24(6): 797–804

[34]

De Luca V, Marineau C, Brisson N. Molecular cloning and analysis of cDNA encoding a plant tryptophan decarboxylase: comparison with animal dopa decarboxylases. Proc Natl Acad Sci USA1989; 86(8): 2582–2586

[35]

McKnight TD, Roessner CA, Devagupta R, Scott AI, Nessler CL. Nucleotide sequence of a cDNA encoding the vacuolar protein strictosidine synthase from Catharanthus roseus. Nucleic Acids Res1990; 18(16): 4939–4939

[36]

Geerlings A, Ibañez MML, Memelink J, van Der Heijden R, Verpoorte R. Molecular cloning and analysis of strictosidine β-D-glucosidase, an enzyme in terpenoid indole alkaloid biosynthesis in Catharanthus roseus. J Biol Chem2000; 275(5): 3051–3056

[37]

Guirimand G, Guihur A, Poutrain P, Héricourt F, Mahroug S, St-Pierre B, Burlat V, Courdavault V. Spatial organization of the vindoline biosynthetic pathway in Catharanthus roseus. J Plant Physiol2011; 168(6): 549–557

[38]

Levac D, Murata J, Kim WS, De Luca V. Application of carborundum abrasion for investigating the leaf epidermis: molecular cloning of Catharanthus roseus 16-hydroxytabersonine-16-O-methyltransferase. Plant J2008; 53(2): 225–236

[39]

St-Pierre B, Laflamme P, Alarco AM, De Luca V. The terminal O-acetyltransferase involved in vindoline biosynthesis defines a new class of proteins responsible for coenzyme A-dependent acyl transfer. Plant J1998; 14(6): 703–713

[40]

Costa MMR, Hilliou F, Duarte P, Pereira LG, Almeida I, Leech M, Memelink J, Barceló AR, Sottomayor M. Molecular cloning and characterization of a vacuolar class III peroxidase involved in the metabolism of anticancer alkaloids in Catharanthus roseus. Plant Physiol2008; 146(2): 403–417

[41]

Yamamoto H, Katano N, Ooi A, Inoue K. Secologanin synthase which catalyzes the oxidative cleavage of loganin into secologanin is a cytochrome P450. Phytochemistry2000; 53(1): 7–12

[42]

Li J, Last RL. The Arabidopsis thaliana trp5 mutant has a feedback-resistant anthranilate synthase and elevated soluble tryptophan. Plant Physiol1996; 110(1): 51–59

[43]

Noé W, Mollenschott C, Berlin J. Tryptophan decarboxylase from Catharanthus roseus cell suspension cultures: purification, molecular and kinetic data of the homogenous protein. Plant Mol Biol1984; 3(5): 281–288

[44]

Pasquali G, Goddijn OJ, de Waal A, Verpoorte R, Schilperoort RA, Hoge JHC, Memelink J. Coordinated regulation of two indole alkaloid biosynthetic genes from Catharanthus roseus by auxin and elicitors. Plant Mol Biol1992; 18(6): 1121–1131

[45]

Menke FL, Champion A, Kijne JW, Memelink J. A novel jasmonate- and elicitor-responsive element in the periwinkle secondary metabolite biosynthetic gene Str interacts with a jasmonate- and elicitor-inducible AP2-domain transcription factor, ORCA2. EMBO J1999; 18(16): 4455–4463

[46]

Besseau S, Kellner F, Lanoue A, Thamm AM, Salim V, Schneider B, Geu-Flores F, Höfer R, Guirimand G, Guihur A, Oudin A, Glevarec G, Foureau E, Papon N, Clastre M, Giglioli-Guivarc’h N, St-Pierre B, Werck-Reichhart D, Burlat V, De Luca V, O’Connor SE, Courdavault V. A pair of tabersonine 16-hydroxylases initiates the synthesis of vindoline in an organ-dependent manner in Catharanthus roseus. Plant Physiol2013; 163(4): 1792–1803

[47]

Schröder G, Unterbusch E, Kaltenbach M, Schmidt J, Strack D, De Luca V, Schröder J. Light-induced cytochrome P450-dependent enzyme in indole alkaloid biosynthesis: tabersonine 16-hydroxylase. FEBS Lett1999; 458(2): 97–102

[48]

Li CY, Leopold AL, Sander GW, Shanks JV, Zhao L, Gibson SI. The ORCA2 transcription factor plays a key role in regulation of the terpenoid indole alkaloid pathway. BMC Plant Biol2013; 13(1): 155

[49]

Suttipanta N, Pattanaik S, Kulshrestha M, Patra B, Singh SK, Yuan L. The transcription factor CrWRKY1 positively regulates the terpenoid indole alkaloid biosynthesis in Catharanthus roseus. Plant Physiol2011; 157(4): 2081–2093

[50]

Martin VJ, Pitera DJ, Withers ST, Newman JD, Keasling JD. Engineering a mevalonate pathway in Escherichia coli for production of terpenoids. Nat Biotechnol2003; 21(7): 796–802

[51]

Ro DK, Paradise EM, Ouellet M, Fisher KJ, Newman KL, Ndungu JM, Ho KA, Eachus RA, Ham TS, Kirby J, Chang MC, Withers ST, Shiba Y, Sarpong R, Keasling JD. Production of the antimalarial drug precursor artemisinic acid in engineered yeast. Nature2006; 440(7086): 940–943

[52]

Ro DK, Ouellet M, Paradise EM, Burd H, Eng D, Paddon CJ, Newman JD, Keasling JD. Induction of multiple pleiotropic drug resistance genes in yeast engineered to produce an increased level of anti-malarial drug precursor, artemisinic acid. BMC Biotechnol2008; 8(1): 83

[53]

Tsuruta H, Paddon CJ, Eng D, Lenihan JR, Horning T, Anthony LC, Regentin R, Keasling JD, Renninger NS, Newman JD. High-level production of amorpha-4,11-diene, a precursor of the antimalarial agent artemisinin, in Escherichia coli. PLoS ONE2009; 4(2): e4489

[54]

Paddon CJ, Westfall PJ, Pitera DJ, Benjamin K, Fisher K, McPhee D, Leavell MD, Tai A, Main A, Eng D, Polichuk DR, Teoh KH, Reed DW, Treynor T, Lenihan J, Fleck M, Bajad S, Dang G, Dengrove D, Diola D, Dorin G, Ellens KW, Fickes S, Galazzo J, Gaucher SP, Geistlinger T, Henry R, Hepp M, Horning T, Iqbal T, Jiang H, Kizer L, Lieu B, Melis D, Moss N, Regentin R, Secrest S, Tsuruta H, Vazquez R, Westblade LF, Xu L, Yu M, Zhang Y, Zhao L, Lievense J, Covello PS, Keasling JD, Reiling KK, Renninger NS, Newman JD. High-level semi-synthetic production of the potent antimalarial artemisinin. Nature2013; 496(7446): 528–532

[55]

Guerra-Bubb J, Croteau R, Williams RM. The early stages of taxol biosynthesis: an interim report on the synthesis and identification of early pathway metabolites. Nat Prod Rep2012; 29(6): 683–696

[56]

Jiang M, Stephanopoulos G, Pfeifer BA. Downstream reactions and engineering in the microbially reconstituted pathway for Taxol. Appl Microbiol Biotechnol2012; 94(4): 841–849

[57]

Dai Z, Liu Y, Huang L, Zhang X. Production of miltiradiene by metabolically engineered Saccharomyces cerevisiae. Biotechnol Bioeng2012; 109(11): 2845–2853

[58]

Zhou YJ, Gao W, Rong Q, Jin G, Chu H, Liu W, Yang W, Zhu Z, Li G, Zhu G, Huang L, Zhao ZK. Modular pathway engineering of diterpenoid synthases and the mevalonic acid pathway for miltiradiene production. J Am Chem Soc2012; 134(6): 3234–3241

[59]

Guo J, Zhou YJ, Hillwig ML, Shen Y, Yang L, Wang Y, Zhang X, Liu W, Peters RJ, Chen X, Zhao ZK, Huang L. CYP76AH1 catalyzes turnover of miltiradiene in tanshinones biosynthesis and enables heterologous production of ferruginol in yeasts. Proc Natl Acad Sci USA2013; 110(29): 12108–12113

RIGHTS & PERMISSIONS

Higher Education Press and Springer-Verlag Berlin Heidelberg

AI Summary AI Mindmap
PDF (238KB)

4711

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/