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Journal Article

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

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Citation

Caputi, L., Franke, J., Farrow, S. C., Chung, K., Payne, R. M. E., Nguyen, T.-D., et al. (2018). Missing enzymes in the biosynthesis of the anticancer drug vinblastine in Madagascar periwinkle. Science, 360(6394), 1235-1238. doi:10.1126/science.aat4100.


Cite as: https://hdl.handle.net/21.11116/0000-0002-D917-0
Abstract
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.