 |
|
Journal articles
Missing enzymes in the biosynthesis of the anticancer drug vinblastine in Madagascar periwinkle
Lorenzo Caputi
1
Jakob Franke
1
Scott Farrow
1
Khoa Chung
1
Richard Payne
1
Trinh-Don Nguyen
1
Thu-Thuy Dang
1
Inês Soares Teto Carqueijeiro
2
Konstantinos Koudounas
2
Thomas Dugé de Bernonville
2
Belinda Ameyaw
1
D. Marc Jones
1
Ivo Jose Curcino Vieira
3
Vincent Courdavault
2
Sarah O’connor
1
Richard Payne 1
Author
Trinh-Don Nguyen 1
Author
Thu-Thuy Dang 1
Author
Inês Soares Teto Carqueijeiro 2
Author
Konstantinos Koudounas 2
Author
Thomas Dugé de Bernonville 2
Author IdHAL : thomas-duge-de-bernonville ORCID : https://orcid.org/0000-0002-2205-2886
Belinda Ameyaw 1
Author
D. Marc Jones 1
Author
1
John Innes Centre [Norwich] (John Innes Centre, Colney, Norwich NR4 7UH - United Kingdom)
2
BBV EA 2106 - Biomolécules et biotechnologies végétales (Université de Tours UFR Sciences Pharmaceutiques 31 avenue Monge 37200 TOURS - France)
- UT - Université de Tours (60 rue du Plat d'Étain, 37020 Tours cedex 1 - France)
3
UENF - Universidade Estadual do Norte Fluminense Darcy Ribeiro (Av. Alberto Lamego, 2000 - Parque Califórnia Campos dos Goytacazes - Brazil)
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.
Document type :
Journal articles
Domain :
Complete list of metadata
https://hal-univ-tours.archives-ouvertes.fr/hal-02527609
Contributor : Sébastien Besseau Connect in order to contact the contributor
Submitted on : Wednesday, April 1, 2020 - 12:01:53 PM
Last modification on : Tuesday, January 11, 2022 - 5:56:06 PM
Contributor : Sébastien Besseau Connect in order to contact the contributor
Submitted on : Wednesday, April 1, 2020 - 12:01:53 PM
Last modification on : Tuesday, January 11, 2022 - 5:56:06 PM
Identifiers
- HAL Id : hal-02527609, version 1
- DOI : 10.1126/science.aat4100
Collections
Citation
Lorenzo Caputi, Jakob Franke, Scott Farrow, Khoa Chung, Richard Payne, et al.. Missing enzymes in the biosynthesis of the anticancer drug vinblastine in Madagascar periwinkle. Science, American Association for the Advancement of Science, 2018, 360 (6394), pp.1235-1239. ⟨10.1126/science.aat4100⟩. ⟨hal-02527609⟩
Metrics
Les métriques sont temporairement indisponibles