The Rauvolfia tetraphylla genome suggests multiple distinct biosynthetic routes for yohimbane monoterpene indole alkaloids.

Autor: Stander EA; Biomolécules et Biotechnologies Végétales, EA2106, Université de Tours, 37200, Tours, France., Lehka B; Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kgs, Lyngby, Denmark., Carqueijeiro I; Biomolécules et Biotechnologies Végétales, EA2106, Université de Tours, 37200, Tours, France., Cuello C; Biomolécules et Biotechnologies Végétales, EA2106, Université de Tours, 37200, Tours, France., Hansson FG; Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kgs, Lyngby, Denmark., Jansen HJ; Future Genomics Technologies, 2333 BE, Leiden, The Netherlands., Dugé De Bernonville T; Biomolécules et Biotechnologies Végétales, EA2106, Université de Tours, 37200, Tours, France.; Limagrain, Centre de Recherche, Route d'Ennezat, Chappes, France., Birer Williams C; Biomolécules et Biotechnologies Végétales, EA2106, Université de Tours, 37200, Tours, France., Vergès V; Biomolécules et Biotechnologies Végétales, EA2106, Université de Tours, 37200, Tours, France., Lezin E; Biomolécules et Biotechnologies Végétales, EA2106, Université de Tours, 37200, Tours, France., Lorensen MDBB; Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark., Dang TT; Department of Chemistry, Irving K. Barber Faculty of Science, University of British Columbia, Kelowna, BC, Canada., Oudin A; Biomolécules et Biotechnologies Végétales, EA2106, Université de Tours, 37200, Tours, France., Lanoue A; Biomolécules et Biotechnologies Végétales, EA2106, Université de Tours, 37200, Tours, France., Durand M; Biomolécules et Biotechnologies Végétales, EA2106, Université de Tours, 37200, Tours, France., Giglioli-Guivarc'h N; Biomolécules et Biotechnologies Végétales, EA2106, Université de Tours, 37200, Tours, France., Janfelt C; Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark., Papon N; Univ Angers, Univ Brest, IRF, SFR ICAT, F-49000, Angers, France., Dirks RP; Future Genomics Technologies, 2333 BE, Leiden, The Netherlands., O'connor SE; Department of Natural Product Biosynthesis, Max Planck Institute for Chemical Ecology, Jena, 07745, Germany. oconnor@ice.mpg.de., Jensen MK; Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kgs, Lyngby, Denmark. mije@dtu.dk., Besseau S; Biomolécules et Biotechnologies Végétales, EA2106, Université de Tours, 37200, Tours, France. sebastien.besseau@univ-tours.fr., Courdavault V; Biomolécules et Biotechnologies Végétales, EA2106, Université de Tours, 37200, Tours, France. vincent.courdavault@univ-tours.fr.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2023 Nov 24; Vol. 6 (1), pp. 1197. Date of Electronic Publication: 2023 Nov 24.
DOI: 10.1038/s42003-023-05574-8
Abstrakt: Monoterpene indole alkaloids (MIAs) are a structurally diverse family of specialized metabolites mainly produced in Gentianales to cope with environmental challenges. Due to their pharmacological properties, the biosynthetic modalities of several MIA types have been elucidated but not that of the yohimbanes. Here, we combine metabolomics, proteomics, transcriptomics and genome sequencing of Rauvolfia tetraphylla with machine learning to discover the unexpected multiple actors of this natural product synthesis. We identify a medium chain dehydrogenase/reductase (MDR) that produces a mixture of four diastereomers of yohimbanes including the well-known yohimbine and rauwolscine. In addition to this multifunctional yohimbane synthase (YOS), an MDR synthesizing mainly heteroyohimbanes and the short chain dehydrogenase vitrosamine synthase also display a yohimbane synthase side activity. Lastly, we establish that the combination of geissoschizine synthase with at least three other MDRs also produces a yohimbane mixture thus shedding light on the complex mechanisms evolved for the synthesis of these plant bioactives.
(© 2023. The Author(s).)
Databáze: MEDLINE
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