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

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.

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 Creators:
Caputi, Lorenzo1, Author              
Franke, Jakob, Author
Farrow, Scott C., Author
Chung, Khoa, Author
Payne, Richard M. E., Author
Nguyen, Trinh-Don, Author
Dang, Thu-Thuy T., Author
Carqueijeiro, Inês Soares Teto, Author
Koudounas, Konstantinos, Author
de Bernonville, Thomas Dugé, Author
Ameyaw, Belinda, Author
Jones, D. Marc, Author
Vieira, Ivo Jose Curcino, Author
Courdavault, Vincent, Author
O'Connor, Sarah E.1, Author              
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1External Organizations, ou_persistent22              

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 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.

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 Dates: 2018-06-152018
 Publication Status: Published in print
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 Identifiers: Other: SOC080
DOI: 10.1126/science.aat4100
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Title: Science
  Other : Science
Source Genre: Journal
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Publ. Info: Washington, D.C. : American Association for the Advancement of Science
Pages: - Volume / Issue: 360 (6394) Sequence Number: - Start / End Page: 1235 - 1238 Identifier: ISSN: 0036-8075
CoNE: https://pure.mpg.de/cone/journals/resource/991042748276600_1