title: De novo production of the plant-derived alkaloid strictosidine in yeast.
abstract: The monoterpene indole alkaloids are a large group of plant-derived specialized metabolites, many of which have valuable pharmaceutical or biological activity. There are ∼3,000 monoterpene indole alkaloids produced by thousands of plant species in numerous families. The diverse chemical structures found in this metabolite class originate from strictosidine, which is the last common biosynthetic intermediate for all monoterpene indole alkaloid enzymatic pathways. Reconstitution of biosynthetic pathways in a heterologous host is a promising strategy for rapid and inexpensive production of complex molecules that are found in plants. Here, we demonstrate how strictosidine can be produced de novo in a Saccharomyces cerevisiae host from 14 known monoterpene indole alkaloid pathway genes, along with an additional seven genes and three gene deletions that enhance secondary metabolism. This system provides an important resource for developing the production of more complex plant-derived alkaloids, engineering of nonnatural derivatives, identification of bottlenecks in monoterpene indole alkaloid biosynthesis, and discovery of new pathway genes in a convenient yeast host.
authors: Department of Biological Chemistry, John Innes Centre, Norwich NR4 7UH, United Kingdom; and.
authors: Stephanie
authors: S
authors: Brown
authors: Équipe d'Accueil EA2106, "Biomolécules et Biotechnologies Végétales," Université François-Rabelais de Tours, 37200 Tours, France.
authors: Marc
authors: M
authors: Clastre
authors: Équipe d'Accueil EA2106, "Biomolécules et Biotechnologies Végétales," Université François-Rabelais de Tours, 37200 Tours, France.
authors: Vincent
authors: V
authors: Courdavault
authors: Department of Biological Chemistry, John Innes Centre, Norwich NR4 7UH, United Kingdom; and Sarah.O'Connor@jic.ac.uk.
authors: Sarah E
authors: SE
authors: O'Connor
mesh_terms: D000426:Alcohol Dehydrogenase / Q000378:metabolism; D053898:Biosynthetic Pathways; D002853:Chromatography, Liquid; D005818:Genetic Engineering; D013058:Mass Spectrometry; D010944:Plants / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000378:metabolism*; D014748:Vinca Alkaloids / Q000096:biosynthesis* / Q000737:chemistry
chemical_list: D014748:Vinca Alkaloids; C021093:strictosidine; D000426:Alcohol Dehydrogenase
keywords: Catharanthus roseus; Saccharomyces cerevisiae; monoterpene indole alkaloid; secologanin; strictosidine