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

Emily Amor Stander, Beata Lehka, Inês Carqueijeiro, Clément Cuello, Frederik G. Hansson, Hans J. Jansen, Thomas Dugé De Bernonville, Caroline Birer Williams, Valentin Vergès, Enzo Lezin, Marcus Daniel Brandbjerg Bohn Lorensen, Thu Thuy Dang, Audrey Oudin, Arnaud Lanoue, Mickael Durand, Nathalie Giglioli-Guivarc’h, Christian Janfelt, Nicolas Papon, Ron P. Dirks, Sarah Ellen O’connor*Michael Krogh Jensen*, Sébastien Besseau*, Vincent Courdavault*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

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.

Original languageEnglish
Article number1197
JournalCommunications Biology
Volume6
Number of pages19
ISSN2399-3642
DOIs
Publication statusPublished - 2023

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