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Missing enzymes in the biosynthesis of the anticancer drug vinblastine in Madagascar periwinkle

Vinblastine, a potent anticancer drug, is produced by Catharanthus roseus (Madagascar periwinkle) in small quantities, and heterologous reconstitution of vinblastine biosynthesis could provide an additional source of this drug. However, the chemistry underlying vinblastine synthesis makes identification of the biosynthetic genes challenging. Here we identify the two missing enzymes necessary for vinblastine biosynthesis in this plant: an oxidase and a reductase that isomerize stemmadenine acetate into dihydroprecondylocarpine acetate, which is then deacetoxylated and cyclized to either catharanthine or tabersonine via two hydrolases characterized herein. The pathways show how plants create chemical diversity and also enable development of heterologous platforms for generation of stemmadenine-derived bioactive compounds.

Authors:   Lorenzo Caputi; Jakob Franke; Scott C. Farrow; Khoa Chung; Richard M. E. Payne; Trinh-Don Nguyen; Thu-Thuy T. Dang; Inês Soares Teto Carqueijeiro; Konstantinos Koudounas; Thomas Dugé de Bernonville; Belinda Ameyaw; D. Marc Jones; Ivo Jose Curcino Vieira; Vincent Courdavault; Sarah E. O’Connor
Journal:   Science
Volume:   360
edition:   6394
Year:   2018
Pages:   1235
DOI:   10.1126/science.aat4100
Publication date:   15-Jun-2018
Facts, background information, dossiers
  • vinblastine
  • enzymes
  • acetate
  • plants
  • Madagascar
  • genes
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