Skip to main content
Log in

Discovery and metabolic engineering of iridoid/secoiridoid and monoterpenoid indole alkaloid biosynthesis

  • Published:
Phytochemistry Reviews Aims and scope Submit manuscript

Abstract

There has been remarkable progress in the discovery of specialized metabolism pathways in the past few years. This has largely been due to the advent of inexpensive high throughput sequencing technologies, improved gene annotation methods and the development of tools for testing candidate genes for their involvement in particular biosynthetic pathways. This review describes the recent discoveries made on new steps in monoterpenoid indole alkaloid (MIA) biosynthesis within Catharanthus roseus. The review also places these discoveries in context of the existing literature on regulation and production of MIAs in whole plants compared to cell and organ cultures.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Modified after Stöckigt et al. (1983)

Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Aerts RJ, De Luca V (1992) Phytochrome is involved in the light-regulation of vindoline biosynthesis in Catharanthus. Plant Physiol 100:1029–1032

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Aerts RJ, Gisi D, Carolis E, De Luca V, Baumann TW (1994) Methyl jasmonate vapor increases the developmentally controlled synthesis of alkaloids in Catharanthus and Cinchona seedlings. Plant J 5:635–643

    Article  CAS  Google Scholar 

  • Arvy M, Imbault N, Naudascher F, Thiersault M, Doireau P (1994) 2,4-D and alkaloid accumulation in periwinkle cell suspensions. Biochimie 76:410–416

    Article  CAS  PubMed  Google Scholar 

  • Asada K, Salim V, Masada-Atsumi S, Edmunds E, Nagatoshi M, Terasaka K, Mizukami H, De Luca V (2013) A 7-deoxyloganetic acid glucosyltransferase contributes a key step in secologanin biosynthesis in Madagascar periwinkle. Plant Cell 25:4123–4134

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Besseau S, Kellner F, Lanoue A, Thamm AMK, 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 (2013) A pair of tabersonine 16-hydroxylases initiates the synthesis of vindoline in an organ-dependent manner in Catharanthus roseus. Plant Physiol 163:1792–1803

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brown RT (1977) “One-pot” biomimetic synthesis of 19-heteroyohimbine alkaloids. J Chem Soc Chem Commun 1977:636–638

    Article  Google Scholar 

  • Brown RT (1979) Biomimetic synthesis of cathenamine and 19-epicathenamine, key intermediates to heteroyohimbine alkaloids. J Chem Soc Chem Commun 20:877–879

    Article  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Cardoso MIL, Meijer AH, Rueb S, Machado JQ, Memelink J, Hoge JHC (1997) A promoter region that controls basal and elicitor-inducible expression levels of the NADPH:cytochrome P450 reductase gene (Cpr) from Catharanthus roseus binds nuclear factor GT-1. Mol Gen Genet 256:674–681

    CAS  PubMed  Google Scholar 

  • Chahed K, Oudin A, Guivarc’h N, Hamdi S, Chénieux J-C, Rideau M, Clastre M (2000) 1-Deoxy-d-xylulose 5-phosphate synthase from periwinkle: cDNA identification and induced gene expression in terpenoid indole alkaloid-producing cells. Plant Physiol Biochem 38:559–566

    Article  CAS  Google Scholar 

  • Chakravarthy S, Tuori RP, D’Ascenzo MD, Fobert PR, Després C, Martin GB (2003) The tomato transcription factor Pti4 regulates defense-related gene expression via GCC box and non-GCC box cis elements. Plant Cell 15:3033–3050

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chatel G, Montiel G, Pré M, Memelink J, Thiersault M, SaintPierre B, Doireau P, Gantet P (2003) CrMYC1, a Catharanthus roseus elicitor and jasmonate responsive bHLH transcription factor that binds the G-box element of the strictosidine synthase gene promoter. J Exp Bot 54:2587–2588

    Article  CAS  PubMed  Google Scholar 

  • Chini A, Fonseca S, Fernández G, Adie B, Chico JM, Lorenzo O, García-Casado G, López-Vidriero I, Lozano FM, Ponce MR, Micol JL, Solano R (2007) The JAZ family of repressors is the missing link in jasmonate signalling. Nature 448:666–671

    Article  CAS  PubMed  Google Scholar 

  • Collu G, Unver N, Peltenburg-Looman AMG, Heijden R, Verpoorte R, Memelink J (2001) Geraniol 10-hydroxylase, a cytochrome P450 enzyme involved in terpenoid indole alkaloid biosynthesis. FEBS Lett 508:215–220

    Article  CAS  PubMed  Google Scholar 

  • Contin A, van der Heijden R, Lefeber AWM, Verpoorte R (1998) The iridoid glucoside secologanin is derived from the novel triose phosphate/pyruvate pathway in a Catharanthus roseus cell culture. FEBS Lett 434:413–416

    Article  CAS  PubMed  Google Scholar 

  • Costa MMR, Hilliou F, Duarte P, Pereira LG, Almeida I, Leech M, Memelink J, Barceló 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, Burlat V, St-Pierre B, Giglioli-Guivarc’h N (2009) Proteins prenylated by type I protein geranylgeranyltransferase act positively on the jasmonate signalling pathway triggering the biosynthesis of monoterpene indole alkaloids in Catharanthus roseus. Plant Cell Rep 28:83–93

    Article  CAS  PubMed  Google Scholar 

  • De Carolis E, De Luca V (1993) Purification, characterization, and kinetic analysis of a 2-oxoglutarate-dependent dioxygenase involved in vindoline biosynthesis from Catharanthus roseus. J Biol Chem 268:5504–5511

    PubMed  Google Scholar 

  • De Carolis E, De Luca V (1994) A novel 2-oxoglutarate-dependent dioxygenase involved in vindoline biosynthesis: characterization, purification and kinetic properties. Plant Cell Tissue Organ Cult 38:281–287

    Article  CAS  Google Scholar 

  • De Luca V, Balsevich J, Tyler RT, Kurz WGW (1987) Characterization of a novel N-methyltransferase (NMT) from Catharanthus roseus plants. Plant Cell Rep 6:458–461

    Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

  • De Luca V, Salim V, Thamm A, Atsumi Masada S, Yu F (2014) Making iridoids/secoiridoids and monoterpenoid indole alkaloids: progress on pathway elucidation. Curr Opin Plant Biol 19:35–42

    Article  PubMed  CAS  Google Scholar 

  • Dethier M, De Luca V (1993) Partial purification of an N-methyltransferase involved in vindoline biosynthesis in Catharanthus roseus. Phytochemistry 32:673–678

    Article  CAS  Google Scholar 

  • Drapeau D, Blanch HW, Wilke CR (1987) Economic assessment of plant cell culture for the production of ajmalicine. Biotechnol Bioeng 30:946–953

    Article  CAS  PubMed  Google Scholar 

  • Dugé de Bernonville T, Clastre M, Besseau S, Oudin A, Burlat V, Glévarec G, Lanoue A, Papon N, Giglioli-Guivarc’h 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  PubMed  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Facchini PJ, Bohlmann J, Covello PS, De Luca V, Mahadevan R, Page JE, Ro D-K, Sensen CW, Storms R, Martin VJJ (2012) Synthetic biosystems for the production of high-value plant metabolites. Trends Biotechnol 30:127–131

    Article  CAS  PubMed  Google Scholar 

  • Galan MC, O’Connor SE (2006) Semi-synthesis of secologanin analogues. Tetrahedron Lett 47:1563–1565

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Geu-Flores F, Sherden NH, Courdavault V, Burlat V, Glenn WS, Wu C, Nims E, Cui Y, O’Connor SE (2012) An alternative route to cyclic terpenes by reductive cyclization in iridoid biosynthesis. Nature 492:138–142

    Article  CAS  PubMed  Google Scholar 

  • Giddings L-A, Liscombe DK, Hamilton JP, Childs KL, DellaPenna D, Buell CR, O’Connor SE (2011) A stereoselective hydroxylation step of alkaloid biosynthesis by a unique cytochrome P450 in Catharanthus roseus. J Biol Chem 286:16751–16757

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ginis O, Courdavault V, Melin C, Lanoue A, Giglioli-Guivarc’h N, St-Pierre B, Courtois M, Oudin A (2012a) Molecular cloning and functional characterization of Catharanthus roseus hydroxymethylbutenyl 4-diphosphate synthase gene promoter from the methyl erythritol phosphate pathway. Mol Biol Rep 39:5433–5447

    Article  CAS  PubMed  Google Scholar 

  • Ginis O, Oudin A, Guirimand G, Chebbi M, Courdavault V, Glévarec G, Papon N, Crèche J, Courtois M (2012b) A type-B response regulator drives the expression of the hydroxymethylbutenyl diphosphate synthase gene in periwinkle. J Plant Physiol 169:1571–1574

    Article  CAS  PubMed  Google Scholar 

  • Glauser G, Grata E, Dubugnon L, Rudaz S, Farmer EE, Wolfender J-L (2008) Spatial and temporal dynamics of jasmonate synthesis and accumulation in Arabidopsis in response to wounding. J Biol Chem 283:16400–16407

    Article  CAS  PubMed  Google Scholar 

  • Gou J-Y, Felippes FF, Liu C-J, Weigel D, Wang J-W (2011) Negative regulation of anthocyanin biosynthesis in Arabidopsis by a miR156-targeted SPL transcription factor. Plant Cell 23:1512–1522

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gu Y-Q, Yang C, Thara VK, Zhou J, Martin GB (2000) Pti4 is induced by ethylene and salicylic acid, and its product is phosphorylated by the Pto kinase. Plant Cell 12:771–785

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guirimand G, Courdavault V, Lanoue A, Mahroug S, Guihur A, Blanc N, Giglioli-Guivarc’h N, St-Pierre B, Burlat V (2010) Strictosidine activation in Apocynaceae: towards a “nuclear time bomb”? BMC Plant Biol 10:182

    PubMed  PubMed Central  Google Scholar 

  • Gundlach H, Müller MJ, Kutchan TM, Zenk MH (1992) Jasmonic acid is a signal transducer in elicitor-induced plant cell cultures. Proc Natl Acad Sci USA 89:2389–2393

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hallahan DL, West JM, Wallsgrove RM, Smiley DW, Dawson GW, Pickett JA, Hamilton JG (1995) Purification and characterization of an acyclic monoterpene primary alcohol:NADP+ oxidoreductase from catmint (Nepeta racemosa). Arch Biochem Biophys 318:105–112

    Article  CAS  PubMed  Google Scholar 

  • Heinstein P, Höfle G, Stöckigt J (1979) Involvement of cathenamine in the formation of N-analogues of indole alkaloids. Planta Med 37:349–357

    Article  CAS  Google Scholar 

  • Hemscheidt T, Zenk MH (1985) Partial purification and characterization of a NADPH dependent tetrahydroalstonine synthase from Catharanthus roseus cell suspension cultures. Plant Cell Rep 4:216–219

    Article  CAS  PubMed  Google Scholar 

  • Ikeda H, Esaki N, Nakai S, Hashimoto K, Uesato S, Soda K, Fujita T (1991) Acyclic monoterpene primary alcohol: NADP+ oxidoreductase of Rauwolfia serpentina cells: the key enzyme in biosynthesis of monoterpene alcohols. J Biochem 109:341–347

    CAS  PubMed  Google Scholar 

  • Irmler S, Schröder G, St-Pierre B, Crouch NP, Hotze M, Schmidt J, Strack D, Matern U, Schröder J (2000) Indole alkaloid biosynthesis in Catharanthus roseus: new enzyme activities and identification of cytochrome P450 CYP72A1 as secologanin synthase. Plant J 24:797–804

    Article  CAS  PubMed  Google Scholar 

  • Ishikawa H, Colby DA, Boger DL (2008) Direct coupling of catharanthine and vindoline to provide vinblastine: total synthesis of (+)- and ent-(−)-vinblastine. J Am Chem Soc 130:420–421

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jun JH, Ha CM, Nam HG (2002) Involvement of the VEP1 gene in vascular strand development in Arabidopsis thaliana. Plant Cell Physiol 43:323–330

    Article  CAS  PubMed  Google Scholar 

  • Kan-Fan C, Husson H-P (1979) Isolation and biomimetic conversion of 4,21-dehydrogeissoschizine. J Chem Soc Chem Commun 1015–1016

  • Katano N, Yamamoto H, Iio R, Inoue K (2001) 7-Deoxyloganin 7-hydroxylase in Lonicera japonica cell cultures. Phytochemistry 58:53–58

    Article  CAS  PubMed  Google Scholar 

  • Kellner F, Kim J, Clavijo BJ, Hamilton JP, Childs KL, Vaillancourt B, Cepela J, Habermann M, Steuernagel B, Clissold L, McLay K, Buell CR, O’Connor SE (2015a) Genome-guided investigation of plant natural product biosynthesis. Plant J 82:680–692

    Article  CAS  PubMed  Google Scholar 

  • Kellner F, Geu-Flores F, Sherden NH, Brown S, Foureau E, Courdavault V, O’Connor SE (2015b) Discovery of a P450-catalyzed step in vindoline biosynthesis: a link between the aspidosperma and eburnamine alkaloids. Chem Commun 51:7626–7628

    Article  CAS  Google Scholar 

  • Kries H, Caputi L, Stevenson CE, Kamileen MO, Sherden NH, Geu-Flores F, Lawson DM, O’Connor SE (2016) Structural determinants of reductive terpene cyclization in iridoid biosynthesis. Nat Chem Biol 12:6–8

    Article  CAS  PubMed  Google Scholar 

  • Krithika R, Srivastav PL, Rani B, Kolet SP, Chopade M, Soniya M, Thulasiram HV (2015) Characterization of 10-hydroxygeraniol dehydrogenase from Catharanthus roseus reveals cascaded enzymatic activity in iridoid biosynthesis. Nat Sci Rep. doi:10.1038/srep08258

    Google Scholar 

  • Laflamme P, St-Pierre B, Luca VD (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 

  • Levac D, Murata J, Kim WS, De Luca VD (2008) Application of carborundum abrasion for investigating the leaf epidermis: molecular cloning of Catharanthus roseus 16-hydroxytabersonine-16-O-methyltransferase. Plant J 53:225–236

    Article  CAS  PubMed  Google Scholar 

  • Li J, Brader G, Palva ET (2004) The WRKY70 transcription factor: a node of convergence for jasmonate-mediated and salicylate-mediated signals in plant defense. Plant Cell 16:319–331

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Li CY, Leopold AL, Sander GW, Shanks JV, Zhao L, Gibson SI (2015) CrBPF1 overexpression alters transcript levels of terpenoid indole alkaloid biosynthetic and regulatory genes. Front Plant Sci 6:1–13

    Google Scholar 

  • Lichtenthaler HK (1999) The 1-dideoxy-d-xylulose-5-phosphate pathway of isoprenoid biosynthesis in plants. Annu Rev Plant Biol 50:47–65

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liscombe DK, Usera AR, O’Connor SE (2010) Homolog of tocopherol C methyltransferases catalyzes N methylation in anticancer alkaloid biosynthesis. Proc Natl Acad Sci USA 107:18793–18798

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lorenzo O, Chico JM, Sánchez-Serrano JJ, Solano R (2004) JASMONATE-INSENSITIVE1 encodes a MYC transcription factor essential to discriminate between different jasmonate-regulated defense responses in Arabidopsis. Plant Cell 16:1938–1950

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Luijendijk TJ, Stevens LH, Verpoorte R (1998) Purification and characterisation of strictosidine β-d-glucosidase from Catharanthus roseus cell suspension cultures. Plant Physiol Biochem 36:419–425

    Article  CAS  Google Scholar 

  • Makhzoum A, Petit-Paly G, Pierre BS, Bernards MA (2011) Functional analysis of the DAT gene promoter using transient Catharanthus roseus and stable Nicotiana tabacum transformation systems. Plant Cell Rep 30:1173–1182

    Article  CAS  PubMed  Google Scholar 

  • McCoy E, Galan MC, O’Connor SE (2006) Substrate specificity of strictosidine synthase. Bioorg Med Chem Lett 16:2475–2478

    Article  CAS  PubMed  Google Scholar 

  • McKnight TD, Roessner CA, Devagupta R, Scott AI, Nessler CL (1990) Nucleotide sequence of a cDNA encoding the vacuolar protein strictosidine synthase from Catharanthus roseus. Nucleic Acids Res 18:4939

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McKnight TD, Bergey DR, Burnett RJ, Nessler CL (1991) Expression of enzymatically active and correctly targeted strictosidine synthase in transgenic tobacco plants. Planta 185:148–152

    Article  CAS  PubMed  Google Scholar 

  • Meehan TD, Coscia CJ (1973) Hydroxylation of geraniol and nerol by a monooxygenase from Vinca rosea. BBRC 53:1043–1048

    CAS  PubMed  Google Scholar 

  • Meijer AH, Cardoso MIL, Voskuilen JT, Waal A, Verpoorte R, Hoge JHC (1993) Isolation and characterization of a cDNA clone from Catharanthus roseus encoding NADPH:cytochrome P450 reductase, an enzyme essential for reactions catalysed by cytochrome P450 monooxygenases in plants. Plant J 4:47–60

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Menke FLH, Parchmann S, Mueller MJ, Kijne JW, Memelink J (1999a) Involvement of the octadecanoid pathway and protein phosphorylation in fungal elicitor-induced expression of terpenoid indole alkaloid biosynthetic genes in Catharanthus roseus. Plant Physiol 119:1289–1296

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Menke FL, Champion A, Kijne JW, Memelink J (1999b) 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 J 18:4455–4463

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miettinen K, Dong L, Navrot N, Schneider T, Burlat V, Pollier J, Woittiez L, van der Krol S, Lugan R, Ilc T, Verpoorte R, Oksman-Caldentey K-M, Marti-noia E, Bouwmeester H, Goossens A, Memelink J, Werck-Reichhart D (2014) The seco-iridoid pathway from Catharanthus roseus. Nat Commun 5:1–12

    Google Scholar 

  • Mizoi J, Shinozaki K, Yamaguchi-Shinozaki K (2012) AP2/ERF family transcription factors in plant abiotic stress responses. Biochim Biophys Acta 1819:86–96

    Article  CAS  PubMed  Google Scholar 

  • Montiel G, Zarei A, Körbes AP, Memelink J (2011) The jasmonate-responsive element from the ORCA3 promoter from Catharanthus roseus is active in Arabidopsis and is controlled by the transcription factor AtMYC2. Plant Cell Physiol 52:578–587

    Article  CAS  PubMed  Google Scholar 

  • Munkert J, Pollier J, Miettinen K, Van Moerkercke A, Payne R, Muller-Uri F, Burlat V, O’Connor SE, Memelink J, Kreis W, Goossens A (2015) Iridoid synthase activity is common among the plant progesterone 5β-reductase family. Mol Plant 8:136–152

    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 20:524–542

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Oudin A, Courtois M, Rideau M, Clastre M (2007) The iridoid pathway in Catharanthus roseus alkaloid biosynthesis. Phytochem Rev 6:259–276

    Article  CAS  Google Scholar 

  • Ouwerkerk PBF, Memelink J (1999) Elicitor-responsive promoter regions in the tryptophan decarboxylase gene from Catharanthus roseus. Plant Mol Biol 39:129–136

    Article  CAS  PubMed  Google Scholar 

  • Ouwerkerk PBF, Trimborn TO, Hilliou F, Memelink J (1999a) Nuclear factors GT-1 and 3AF1 interact with multiple sequences within the promoter of the Tdc gene from Madagascar periwinkle: GT-1 is involved in UV light-induced expression. Mol Gen Genet 261:610–622

    Article  CAS  PubMed  Google Scholar 

  • Ouwerkerk PBF, Hallard D, Verpoorte R, Memelink J (1999b) Identification of UV-B light-responsive regions in the promoter of the tryptophan decarboxylase gene from Catharanthus roseus. Plant Mol Biol 41:491–503

    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 7:1–14

    Google Scholar 

  • Papon N, Bremer J, Vansiri A, Andreu F, Rideau M, Crèche J (2005) Cytokinin and ethylene control indole alkaloid production at the level of the MEP/terpenoid pathway in Catharanthus roseus suspension cells. Planta Med 71:572–574

    Article  CAS  PubMed  Google Scholar 

  • Pasquali G, Goddijn OJM, Waal Ad, Verpoorte R, Schilperoort RA, Hoge JHC, Memelink J (1992) Coordinated regulation of two indole alkaloid biosynthetic genes from Catharanthus roseus by auxin and elicitors. Plant Mol Biol 18:1121–1131

    Article  CAS  PubMed  Google Scholar 

  • Pasquali G, Erven AS, Ouwerkerk PB, Menke FL, Memelink J (1999) The promoter of the strictosidine synthase gene from periwinkle confers elicitor-inducible expression in transgenic tobacco and binds nuclear factors GT-1 and GBF. Plant Mol Biol 39:1299–1310

    Article  CAS  PubMed  Google Scholar 

  • Patra B, Schluttenhofer C, Wu Y, Pattanaik S, Yuan L (2013) Transcriptional regulation of secondary metabolite biosynthesis in plants. Biochim Biophys Acta 1829:1236–1247

    Article  CAS  PubMed  Google Scholar 

  • Pauw B, Memelink J (2004) Jasmonate-responsive gene expression. J Plant Growth Regul 23:200–210

    Article  CAS  Google Scholar 

  • Pauw B, Hilliou FAO, Martin VS, Chatel G, de Wolf CJF, Champion A, Pré M, van Duijn B, Kijne JW, van der Fits L, 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 

  • Pauwels L, Barbero GF, Geerinck J, Tilleman S, Grunewald W, Pérez AC, Chico JM, Bossche RV, Sewell J, Gil E, García-Casado G, Witters E, Inzé D, Long JA, De Jaeger G, Solano R, Goossens A (2010) NINJA connects the co-repressor TOPLESS to jasmonate signalling. Nature 464:788–791

    Article  CAS  PubMed  PubMed Central  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 

  • Pfitzner A, Stöckigt J (1982) Partial purification and characterization of geissoschizine dehydrogenase from suspension cultures of Catharanthus roseus. Phytochemistry 21:1585–1588

    Article  CAS  Google Scholar 

  • Poutrain P, Mazars C, Thiersault M, Rideau M, Pichon O (2009) Two distinct intracellular Ca2+-release components act in opposite ways in the regulation of the auxin-dependent MIA biosynthesis in Catharanthus roseus cells. J Exp Bot 60:1387–1398

    Article  CAS  PubMed  Google Scholar 

  • Power R, Kurz WGW, De Luca V (1990) Purification and characterization of acetylcoenzyme A: deacetylvindoline 4-O-acetyltransferase from Catharanthus roseus. Arch Biochem Biophys 279:370–376

    Article  CAS  PubMed  Google Scholar 

  • 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. Proc Natl Acad Sci USA 112:6224–6229

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qureshi AA, Scott AI (1968) Interconversion of Corynanthe, Aspidosperma, and Iboga alkaloids. A model for indole alkaloid biosynthesis. Chem Commun 12:945–946

    Google Scholar 

  • Ramos-Valdivia AC, Heijden Rvd, Verpoorte R (1997) Isopentenyl diphosphate isomerase: a core enzyme in isoprenoid biosynthesis. A review of its biochemistry and function. Nat Prod Rep 14:591–603

    Article  CAS  PubMed  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 AMK, 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 USA 107:15287–15292

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roewer IA, Cloutier N, Nessler CL, Luca VD (1992) Transient induction of tryptophan decarboxylase (TDC) and strictosidine synthase (SS) genes in cell suspension cultures of Catharanthus roseus. Plant Cell Rep 11:86–89

    Article  CAS  PubMed  Google Scholar 

  • Roja G, Heble MR (1996) Indole alkaloids in clonal propagules of Rauwolfia serpentina Benthe ex Kurz. Plant Cell Tissue Organ Cult 44:111–115

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Salim V, Yu F, Altarejos J, De Luca V (2013) Virus induced gene silencing identifies Catharanthus roseus 7-deoxyloganic acid-7-hydroxylase, a step in iridoid and monoterpene indole alkaloid biosynthesis. Plant J 76:754–765

    Article  CAS  PubMed  Google Scholar 

  • Salim V, Wiens B, Masada-Atsumi S, Yu F, De Luca V (2014) 7-Deoxyloganetic acid synthase catalyzes a key 3 step oxidation to form 7-deoxyloganetic acid in Catharanthus roseus iridoid biosynthesis. Phytochemistry 101:23–31

    Article  CAS  PubMed  Google Scholar 

  • Sanchez-Iturbe PG, Galaz-Avalos RM, Loyola-Vargas VM (2005) De-termination and partial purification of 10-oxogeranial: iridodial cyclase an enzyme catalyzing the synthesis of iridodial/nepetalactol from Catharanthus roseus hairy roots. Phyton 54:55–69

    Google Scholar 

  • Schläger S, Dräger B (2016) Exploiting plant alkaloids. Curr Opin Biotechnol 37:155–164

    Article  PubMed  CAS  Google Scholar 

  • Schröder G, Unterbusch E, Kaltenbach M, Schmidt J, Strack D, De Luca V, Schröder J (1999) Light-induced cytochrome P450-dependent enzyme in indole alkaloid biosynthesis: tabersonine 16-hydroxylase. FEBS Lett 458:97–102

    Article  PubMed  Google Scholar 

  • Sheard LB, Tan X, Mao H, Withers J, Ben-Nissan G, Hinds TR, Kobayashi Y, Hsu F-F, Sharon M, Browse J, He SY, Rizo J, Howe GA, Zheng N (2010) Jasmonate perception by inositol-phosphate-potentiated COI1-JAZ co-receptor. Nature 468:400–405

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sibéril Y, Benhamron S, Memelink J, Giglioli-Guivarc’h N, Thiersault M, Bois-son B, Doireau P, Gantet P (2001) Catharanthus roseus G-box binding factors 1 and 2 act as repressors of strictosidine synthase gene expression in cell cultures. Plant Mol Biol 45:477–488

    Article  PubMed  Google Scholar 

  • 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 MJC, Memelink J, Clastre M (2013) Characterization of the plastidial geraniol synthase from Madagascar periwinkle which initiates the monoterpenoid branch of the alkaloid pathway in internal phloem associated parenchyma. Phytochemistry 85:36–43

    Article  CAS  PubMed  Google Scholar 

  • Stavrinides A, Tatsis EC, Foureau E, Caputi L, Kellner F, Courdavault V, O’Connor SE (2015) Unlocking the diversity of alkaloids in Catharanthus roseus: nuclear localization suggests metabolic channeling in secondary metabolism. Chem Biol 22:336–341

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stevens L, Blom T, Verpoorte R (1993) Subcellular localization of tryptophan decarboxylase, strictosidine synthase and strictosidine glucosidase in suspension cultured cells of Catharanthus roseus and Tabernaemontana divaricata. Plant Cell Rep 12:573–576

    Article  CAS  PubMed  Google Scholar 

  • Stöckigt J (1978) Indirect involvement of geissoschizine in the biosynthesis of ajmalicine and related alkaloids. J Chem Soc Chem Commun 24:1097–1099

    Article  Google Scholar 

  • Stöckigt J, Höfle G, Pfitzner A (1980) Mechanism of the biosynthetic conversion of geissoschizine to 19-epi-ajmalicine in. Tetrahedron Lett 21:1925–1926

    Article  Google Scholar 

  • Stöckigt J, Hemscheidt T, Höfle G, Heinstein P, Formacek V (1983) Steric course of hydrogen transfer during enzymatic formation of 3α-heteroyohimbine alkaloids. Biochemistry 22:3448–3452

    Article  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

    CAS  PubMed  PubMed Central  Google Scholar 

  • St-Pierre B, Laflamme P, Alarco A-M, De Luca V (1998) The terminal O-acetyltransferase involved in vindoline biosynthesis defines a new class of proteins responsible for coenzyme A-dependent acyl transfer. Plant J 14:703–713

    Article  CAS  PubMed  Google Scholar 

  • St-Pierre B, Vázquez-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 

  • Suttipanta N (2011) Characterization of G10H promoter and isolation of WRKY transcription factors involved in Catharanthus terpenoid indole alkaloid biosynthesis pathway. Ph.D. thesis, University of Kentucky, Kentucky, USA

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Szabo G (2008) Molecular evolutionary lines in the formation of indole alkaloids derived from secologanin. Arkivoc 3:167–181

    Google Scholar 

  • Teoh KH, Gorman EB, McKnight TD (2000) Characterization and cloning of 10-hydroxygeraniol oxidoreductase. American Society of Plant Biolgists, Plant Biology 2000, Abstract # 272

  • Thines B, Katsir L, Melotto M, Niu Y, Mandaokar A, Liu G, Nomura K, He SY, Howe GA, Browse J (2007) JAZ repressor proteins are targets of the SCFCOI1 complex during jasmonate signalling. Nature 448:661–665

    Article  CAS  PubMed  Google Scholar 

  • Treimer JF, Zenk MH (1978) Enzymic synthesis of corynanthe-type alkaloids in cell cultures of Catharanthus roseus: quantitation by radioimmunoassay. Phytochemistry 17:227–231

    Article  CAS  Google Scholar 

  • Uesato S, Ikeda H, Fujita T, Inouye H, Zenk MH (1987) Elucidation of iridodial formation mechanism—partial purification and characterization of the novel monoterpene cyclase from Rauwolfia serpentina cell suspension cultures. Tetrahedron Lett 28:4431–4434

    Article  CAS  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, Memelink J (2001) The jasmonate-inducible AP2/ERF-domain transcription factor ORCA3 activates gene expression via interaction with a jasmonate-responsive promoter element. Plant J 25:43–53

    Article  PubMed  Google Scholar 

  • Van der Fits L, Zhang H, Menke FL, Deneka M, Memelink J (2000) A Catharanthus roseus BPF-1 homologue interacts with an elicitor-responsive region of the secondary metabolite biosynthetic gene Str and is induced by elicitor via a JA-independent signal transduction pathway. Plant Mol Biol 44:675–685

    Article  PubMed  Google Scholar 

  • Van der 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 

  • Van Moerkercke A, Steensma P, Schweizer F, Pollier J, Gariboldi I, Payne R, Vanden Bossche R, Miettinen K, Espoz J, Purnama PC, Kellner F, Seppänen-Laakso T, O’Connor SE, Rischer H, Memelink J, Goossens A (2015) The bHLH transcription factor BIS1 controls the iridoid branch of the monoterpenoid indole alkaloid pathway in Catharanthus roseus. Proc Natl Acad Sci USA 112:8130–8135

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Vázquez-Flota FA, De Luca V (1998) Developmental and light regulation of desacetoxyvindoline 4-hydroxylase in Catharanthus roseus (L.) G. Don. evidence of a multilevel regulatory mechanism. Plant Physiol 117:1351–1361

    Article  PubMed  PubMed Central  Google Scholar 

  • Vázquez-Flota F, Carolis ED, Alarco A-M, Luca VD (1997) Molecular cloning and characterization of desacetoxyvindoline-4-hydroxylase, a 2-oxoglutarate dependent-dioxygenase involved in the biosynthesis of vindoline in Catharanthus roseus (L.) G. Don. Plant Mol Biol 34:935–948

    Article  PubMed  Google Scholar 

  • Vázquez-Flota FA, St-Pierre B, De Luca V (2000) Light activation of vindoline biosynthesis does not require cytomorphogenesis in Catharanthus roseus seedlings. Phytochemistry 55:531–536

    Article  PubMed  Google Scholar 

  • Vázquez-Flota F, Carrillo-Pech M, Minero-García Y, de Lourdes Miranda-Ham M (2004) Alkaloid metabolism in wounded Catharanthus roseus seedlings. Plant Physiol Biochem 42:623–628

    Article  PubMed  CAS  Google Scholar 

  • Veau B, Courtois M, Oudin A, Chénieux J-C, Rideau M, Clastre M (2000) Cloning and expression of cDNAs encoding two enzymes of the MEP pathway in Catharanthus roseus. Biochim Biophys Acta 1517:159–163

    Article  CAS  PubMed  Google Scholar 

  • Vom Endt D, Silva MSe, Kijne JW, Pasquali G, Memelink J (2007) Identification of a bipartite jasmonate-responsive promoter element in the Catharanthus roseus ORCA3 transcription factor gene that interacts specifically with AT-Hook DNA-binding proteins. Plant Physiol 144:1680–1689

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang Q, Yuan F, Pan Q, Li M, Wang G, Zhao J, Tang K (2010) Isolation and functional analysis of the Catharanthus roseus deacetylvindoline-4-O-acetyltransferase gene promoter. Plant Cell Rep 29:185–192

    Article  PubMed  CAS  Google Scholar 

  • Wasternack C (2007) Jasmonates: an update on biosynthesis, signal transduction and action in plant stress response, growth and development. Ann Bot 100:681–697

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Williams ME, Foster R, Chua NH (1992) Sequences flanking the hexameric G-box core CACGTG affect the specificity of protein binding. Plant Cell 4:485–496

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xiao M, Zhang Y, Chen X, Lee E-J, Barber CJS, Chakrabarty R, Desgagné-Penix I, Haslam TM, Kim Y-B, Liu E, MacNevin G, Masada-Atsumi S, Reed DW, Stout JM, Zerbe P, Zhang Y, Bohlmann J, Covello PS, De Luca V, Page JE, Ro D-K, Martin VJJ, Facchini PJ, Sensen CW (2013) Transcriptome analysis based on next-generation sequencing of non-model plants producing specialized metabolites of biotechnological interest. J Biotechnol 166:122–134

    Article  CAS  PubMed  Google Scholar 

  • Yahia A, Kevers C, Gaspar T, Chénieux J-C, Rideau M, Crèche J (1998) Cytokinins and ethylene stimulate indole alkaloid accumulation in cell suspension cultures of Catharanthus roseus by two distinct mechanisms. Plant Sci 133:9–15

    Article  CAS  Google Scholar 

  • Yamamoto H, Katano N, Ooi A, Inoue K (2000) Secologanin synthase which catalyzes the oxidative cleavage of loganin into secologanin is a cytochrome P450. Phytochemistry 53:7–12

    Article  CAS  PubMed  Google Scholar 

  • Yamamoto S, Nakano T, Suzuki K, Shinshi H (2004) Elicitor-induced activation of transcription via W box-related cis-acting elements from a basic chitinase gene by WRKY transcription factors in tobacco. Biochim Biophys Acta 1679:279–287

    Article  CAS  PubMed  Google Scholar 

  • Yang KY, Moon YH, Choi KH, Kim YH, Eun MY, Guh JO, Kim KC, Cho BH (1997) Structure and expression of the AWI 31 gene specifically induced by wounding in Arabidopsis thaliana. Mol Cell 7:131–135

    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 

  • Yu F, De Luca V (2013) ATP-binding cassette transporter controls leaf surface secretion of anticancer drug components in Catharanthus roseus. Proc Natl Acad Sci USA 110:15830–15835

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang H, Hedhili S, Montiel G, Zhang Y, Chatel G, Pré 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 

Download references

Acknowledgments

This work was supported by a Natural Sciences and Engineering Research Council of Canada Discovery Grant (V.D.L.), Canada Research Chairs (V.D.L.).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Vincenzo De Luca.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Thamm, A.M.K., Qu, Y. & De Luca, V. Discovery and metabolic engineering of iridoid/secoiridoid and monoterpenoid indole alkaloid biosynthesis. Phytochem Rev 15, 339–361 (2016). https://doi.org/10.1007/s11101-016-9468-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11101-016-9468-y

Keywords

Navigation