Details
| Original language | English |
|---|---|
| Pages (from-to) | 1235-1239 |
| Number of pages | 5 |
| Journal | SCIENCE |
| Volume | 360 |
| Issue number | 6394 |
| Early online date | 3 May 2018 |
| Publication status | Published - 15 Jun 2018 |
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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In: SCIENCE, Vol. 360, No. 6394, 15.06.2018, p. 1235-1239.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Missing enzymes in the biosynthesis of the anticancer drug vinblastine in Madagascar periwinkle
AU - Caputi, Lorenzo
AU - Franke, Jakob
AU - Farrow, Scott C.
AU - Chung, Khoa
AU - Payne, Richard M.E.
AU - Nguyen, Trinh Don
AU - Dang, Thu Thuy T.
AU - Teto Carqueijeiro, Inês Soares
AU - Koudounas, Konstantinos
AU - De Bernonville, Thomas Dugé
AU - Ameyaw, Belinda
AU - Jones, D. Marc
AU - Curcino Vieira, Ivo Jose
AU - Courdavault, Vincent
AU - O’Connor, Sarah E.
PY - 2018/6/15
Y1 - 2018/6/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85046700245&partnerID=8YFLogxK
U2 - 10.1126/science.aat4100
DO - 10.1126/science.aat4100
M3 - Article
C2 - 29724909
AN - SCOPUS:85046700245
VL - 360
SP - 1235
EP - 1239
JO - SCIENCE
JF - SCIENCE
SN - 0036-8075
IS - 6394
ER -