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

  • Santé-Sciences-Technologie,
  • Pharmacie,

du 24 novembre 2023 au 1 janvier 2026


Site Grandmont

EA2106 BBV - Biomolécules et Biotechnologies végétales

Our results published in Communications Biology, a Portfolio Nature journal, pave the way towards alkaloid bioproduction in yeast, and among them, yohimbine, rauwolscine, corynathine (and their derivatives), therapetuic molecules with selective affinity for α2-adrenergic and α1-adrenergic receptors,

This work was performed in collaboration with our partners from Max Planck for chemical ecology, Technical University of Denmark, Future Genomics Technologies (The Netherlands). It was supported by EU Horizon H2020 and innovation program MIAMi,  the Région Centre Val de Loire and ANR.

Stander EA, Lehka B, Carqueijeiro I, Cuello C, Hansson FG, Jansen HJ, Dugé De Bernonville T, Birer Williams C, Vergès V, Lezin E, Lorensen MDBB, Dang TT, Oudin A, Lanoue A, Durand M, Giglioli-Guivarc'h N, Janfelt C, Papon N, Dirks RP, O'connor SE, Jensen MK, Besseau S, Courdavault V. The Rauvolfia tetraphylla genome suggests multiple distinct biosynthetic routes for yohimbane monoterpene indole alkaloids. Commun Biol. 2023 Nov 24;6(1):1197. doi: 10.1038/s42003-023-05574-8.


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.