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

Publikation: Beitrag in Fachzeitschrift › Artikel › Forschung › Peer-Review

Autoren

  • 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

Organisationseinheiten

Externe Organisationen

  • John Innes Centre
  • University of Oxford
  • Universität François Rabelais Tours
  • Lancaster University
  • Laboratório de Ciências Químicas (LCQUI)
Forschungs-netzwerk anzeigen

Details

OriginalspracheEnglisch
Seiten (von - bis)1235-1239
Seitenumfang5
FachzeitschriftSCIENCE
Jahrgang360
Ausgabenummer6394
Frühes Online-Datum3 Mai 2018
PublikationsstatusVeröffentlicht - 15 Juni 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.

ASJC Scopus Sachgebiete

Zitieren

Missing enzymes in the biosynthesis of the anticancer drug vinblastine in Madagascar periwinkle. / Caputi, Lorenzo; Franke, Jakob; Farrow, Scott C. et al.
in: SCIENCE, Jahrgang 360, Nr. 6394, 15.06.2018, S. 1235-1239.

Publikation: Beitrag in Fachzeitschrift › Artikel › Forschung › Peer-Review

Caputi, L, Franke, J, Farrow, SC, Chung, K, Payne, RME, Nguyen, TD, Dang, TTT, Teto Carqueijeiro, IS, Koudounas, K, De Bernonville, TD, Ameyaw, B, Jones, DM, Curcino Vieira, IJ, Courdavault, V & O’Connor, SE 2018, 'Missing enzymes in the biosynthesis of the anticancer drug vinblastine in Madagascar periwinkle', SCIENCE, Jg. 360, Nr. 6394, S. 1235-1239. https://doi.org/10.1126/science.aat4100
Caputi, L., Franke, J., Farrow, S. C., Chung, K., Payne, R. M. E., Nguyen, T. D., Dang, T. T. T., Teto Carqueijeiro, I. S., Koudounas, K., De Bernonville, T. D., Ameyaw, B., Jones, D. M., Curcino Vieira, I. J., Courdavault, V., & O’Connor, S. E. (2018). Missing enzymes in the biosynthesis of the anticancer drug vinblastine in Madagascar periwinkle. SCIENCE, 360(6394), 1235-1239. https://doi.org/10.1126/science.aat4100
Caputi L, Franke J, Farrow SC, Chung K, Payne RME, Nguyen TD et al. Missing enzymes in the biosynthesis of the anticancer drug vinblastine in Madagascar periwinkle. SCIENCE. 2018 Jun 15;360(6394):1235-1239. Epub 2018 Mai 3. doi: 10.1126/science.aat4100
Caputi, Lorenzo ; Franke, Jakob ; Farrow, Scott C. et al. / Missing enzymes in the biosynthesis of the anticancer drug vinblastine in Madagascar periwinkle. in: SCIENCE. 2018 ; Jahrgang 360, Nr. 6394. S. 1235-1239.
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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.

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