The iridoid pathway in Catharanthus roseus alkaloid biosynthesis

Abstract

The Apocynaceae Catharanthus roseus accumulates a number of monoterpene indole alkaloids (MIAs) that originate from the coupling of the indole and the iridoid pathways. The latter pathway is usually considered as limiting for MIA biosynthesis, but evidence is now strong that the precursors tryptamine (from the indole pathway) and secologanin (from the iridoid pathway) have to be provided within the cells in a concerted manner for sustained MIA synthesis. Secologanin is formed from isopentenyl diphosphate (IPP) in a number of steps, some of which are still unknown. However significant progress has been obtained recently with the characterisation of cDNAs encoding secologanin synthase and the two constituents of geraniol 10-hydroxylase (G10H). IPP itself is formed through both the plastidial methyl-erythritol phosphate (MEP) pathway and the cytosolic mevalonate (MVA) pathway. The MEP pathway comprises 7 steps of which 4 have been identified at the molecular level in C. roseus. This pathway plays a major role in the production of MIAs, but there is now evidence that the MVA pathway serves as a minor source of precursors for iridoid biosynthesis and/or contributes (through protein prenylation) to a fine regulation of the MEP gene expression. G10H is one of the key enzymes of the MIA pathway and the upregulation of the gene activity concomitantly with an increase in G10H activity and MIA production have been reported with various hormones and elicitors. Since regulatory genes encoding transcription factors acting on several genes of the MEP and terpenoid pathways are beginning to be characterised, metabolic engineering of the iridoid pathway could be a promising approach to control the metabolite flux towards secologanin and MIA production through biotechnological applications in the future.Keywords Madagascar periwinkle Á Cross talk Á Methyl-erythritol phosphate pathway Á Mevalonate pathway Á Secologanin-derived monoterpene indole alkaloids Á Terpenoid pathway Abbreviations AACT Acetoacetyl-CoA thiolase ADH (monoterpene primary) Alcohol dehydrogenase CDP-ME 4-Diphosphocytidyl-2-C-methyl-D-erythritol CMK 4-Diphosphocytidyl-2-C-methyl-D-erythritol kinase A. Oudin (&) Á M. Courtois Á M. Rideau Á M. Clastre EA 2106,

Opium poppy and Madagascar periwinkle: model non‐model systems to investigate alkaloid biosynthesis in plants

“…Several reviews have also been published on the analysis (Hisiger and Jolicoeur, 2007), chemistry (O'Connor and Maresh, 2006), biosynthesis (El-Sayed and Verpoorte, 2007;Hedhili et al, 2007;LoyolaVargas et al, 2007;Oudin et al, 2007a), regulation (Memelink and Gantet, 2007), intra-cellular, inter-cellular and organ-specific compartmentation (Mahroug et al, 2007), plant cell culture-based production (Zhao and Verpoorte, 2007), biotechnological production (Zá rate and , functional genomics (Goossens and Rischer, 2007) and transport (Roytrakul and Verpoorte, 2007) of MIAs in C. roseus. Together, these reviews reflect the profusion of scientific achievements that highlight opium poppy and C. roseus as two of the most thoroughly investigated medicinal plants.…”

Cloning and Functional Analysis of Geraniol 10-Hydroxylase, a Cytochrome P450 fromSwertia mussotiiFranch

“…5,9,12) CYP76B1 of H. tuberosus was identified as 7-ethoxycoumarin O-deethylase, and is induced by xenobiotics. 23) CYP76B6 of C. roseus hydroxylates geraniol to 10-hydroxygeraniol both in vitro and in vivo.…”

“…[5][6][7][8][9][10][11][12] CYP76B6 of C. roseus is significant in indole alkaloid synthesis. [5][6][7][8][9][10][11][12] Here, overexpression of SmG10H in transgenic plants promoted the accumulation of its downstream end-product swertiamarin (Fig. 9e, f).…”

“…The iridoid biosynthetic pathway has not been characterized in detail. [5][6][7] The methylerythritol phosphate (MEP) pathway plays a major role in the production of iridoids, while the mevalonic acid (MVA) pathway serves as a minor source of precursors for iridoid biosynthesis (Fig. 1).…”

“…1.14.14.1), a P450 in the CYP76B subfamily, hydroxylates geraniol at the C-10 position and is thought to be involved in the synthesis of indole alkaloids and iridoid monoterpenoid. [5][6][7][8][9][10][11][12] Similar G10H proteins have been extensively analyzed in several other species. [5][6][7][8][9] These studies have been focused on the importance of G10H in indole alkaloid synthesis, [8][9][10][11][12] but there is no longer a lack of research on iridoid monoterpenoid synthesis at the molecular level.…”