title: Phytochemical genomics of the Madagascar periwinkle: Unravelling the last twists of the alkaloid engine.
abstract: The Madagascar periwinkle produces a large palette of Monoterpenoid Indole Alkaloids (MIAs), a class of complex alkaloids including some of the most valuable plant natural products with precious therapeutical values. Evolutionary pressure on one of the hotspots of biodiversity has obviously turned this endemic Malagasy plant into an innovative alkaloid engine. Catharanthus is a unique taxon producing vinblastine and vincristine, heterodimeric MIAs with complex stereochemistry, and also manufactures more than 100 different MIAs, some shared with the Apocynaceae, Loganiaceae and Rubiaceae members. For over 60 years, the quest for these powerful anticancer drugs has inspired biologists, chemists, and pharmacists to unravel the chemistry, biochemistry, therapeutic activity, cell and molecular biology of Catharanthus roseus. Recently, the "omics" technologies have fuelled rapid progress in deciphering the last secret of strictosidine biosynthesis, the central precursor opening biosynthetic routes to several thousand MIA compounds. Dedicated C. roseus transcriptome, proteome and metabolome databases, comprising organ-, tissue- and cell-specific libraries, and other phytogenomic resources, were developed for instance by PhytoMetaSyn, Medicinal Plant Genomic Resources and SmartCell consortium. Tissue specific library screening, orthology comparison in species with or without MIA-biochemical engines, clustering of gene expression profiles together with various functional validation strategies, largely contributed to enrich the toolbox for plant synthetic biology and metabolic engineering of MIA biosynthesis.
authors.affiliation: Université François-Rabelais de Tours, EA2106 "Biomolécules et Biotechnologies Végétales", Tours, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Dugé de Bernonville
authors.affiliation: Université François-Rabelais de Tours, EA2106 "Biomolécules et Biotechnologies Végétales", Tours, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Clastre
authors.affiliation: Université François-Rabelais de Tours, EA2106 "Biomolécules et Biotechnologies Végétales", Tours, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Besseau
authors.affiliation: Université François-Rabelais de Tours, EA2106 "Biomolécules et Biotechnologies Végétales", Tours, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Oudin
authors.affiliation: Université de Toulouse, UPS, UMR 5546, Laboratoire de Recherche en Sciences Végétales, BP 42617 Auzeville, F-31326 Castanet-Tolosan, France; CNRS, UMR 5546, BP 42617 Auzeville, F-31326 Castanet-Tolosan, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Burlat
authors.affiliation: Université François-Rabelais de Tours, EA2106 "Biomolécules et Biotechnologies Végétales", Tours, France.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Glévarec
authors.affiliation: Université François-Rabelais de Tours, EA2106 "Biomolécules et Biotechnologies Végétales", Tours, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Lanoue
authors.affiliation: Université François-Rabelais de Tours, EA2106 "Biomolécules et Biotechnologies Végétales", Tours, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Papon
authors.affiliation: Université François-Rabelais de Tours, EA2106 "Biomolécules et Biotechnologies Végétales", Tours, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Giglioli-Guivarc'h
authors.affiliation: Université François-Rabelais de Tours, EA2106 "Biomolécules et Biotechnologies Végétales", Tours, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: St-Pierre
authors.affiliation: Université François-Rabelais de Tours, EA2106 "Biomolécules et Biotechnologies Végétales", Tours, France. Electronic address: vincent.courdavault@univ-tours.fr.
authors.forename: Vincent
authors.initials: V
authors.lastname: Courdavault
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D030008:Catharanthus / Q000737:chemistry / Q000235:genetics*; D023281:Genomics; D008270:Madagascar; D015394:Molecular Structure; D064209:Phytochemicals / Q000235:genetics; D046948:Secologanin Tryptamine Alkaloids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D059467:Transcriptome / Q000235:genetics; D014747:Vinblastine / Q000378:metabolism; D014748:Vinca Alkaloids / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D064209:Phytochemicals; D046948:Secologanin Tryptamine Alkaloids; D014748:Vinca Alkaloids; C021093:strictosidine; D014747:Vinblastine
keywords: Alkaloids; Apocynaceae; Catharanthus roseus; High throughput sequencing; Madagascar periwinkle; Phytochemical genomics; Transcriptomics