The Rauvolfia tetraphylla genome suggests multiple distinct biosynthetic routes for yohimbane monoterpene indole alkaloids
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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.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | 1197 |
| Tidsskrift | Communications Biology |
| Vol/bind | 6 |
| Udgave nummer | 1 |
| Antal sider | 19 |
| ISSN | 2399-3642 |
| DOI | |
| Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:
This work was supported by EU Horizon 2020 research and innovation program [MIAMi project-Grant agreement N°814645]; BII Foundation (grant nos. NNF19OC0055591 and NNF20SA0067054); ARD CVL Biopharmaceutical program of the Région Centre-Val de Loire [ETOPOCentre project]; ANR [project MIACYC – ANR-20-CE43-0010]; and APR-IR of the Région Centre-Val de Loire [BioSynNAC project]. The authors benefited from the use of the cluster at the Centre de Calcul Scientifique en région Centre-Val de Loire. We also thank the “Plateforme d’Analyse Protéomique de Paris Sud-Ouest” (PAPPSO) for proteomic analysis.
Funding Information:
This work was supported by EU Horizon 2020 research and innovation program [MIAMi project-Grant agreement N°814645]; BII Foundation (grant nos. NNF19OC0055591 and NNF20SA0067054); ARD CVL Biopharmaceutical program of the Région Centre-Val de Loire [ETOPOCentre project]; ANR [project MIACYC – ANR-20-CE43-0010]; and APR-IR of the Région Centre-Val de Loire [BioSynNAC project]. The authors benefited from the use of the cluster at the Centre de Calcul Scientifique en région Centre-Val de Loire. We also thank the “Plateforme d’Analyse Protéomique de Paris Sud-Ouest” (PAPPSO) for proteomic analysis.
Publisher Copyright:
© 2023, The Author(s).
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