TY - JOUR
T1 - The Rauvolfia tetraphylla genome suggests multiple distinct biosynthetic routes for yohimbane monoterpene indole alkaloids
AU - Stander, Emily Amor
AU - Lehka, Beata
AU - Carqueijeiro, Inês
AU - Cuello, Clément
AU - Hansson, Frederik G.
AU - Jansen, Hans J.
AU - Dugé De Bernonville, Thomas
AU - Birer Williams, Caroline
AU - Vergès, Valentin
AU - Lezin, Enzo
AU - Lorensen, Marcus Daniel Brandbjerg Bohn
AU - Dang, Thu Thuy
AU - Oudin, Audrey
AU - Lanoue, Arnaud
AU - Durand, Mickael
AU - Giglioli-Guivarc’h, Nathalie
AU - Janfelt, Christian
AU - Papon, Nicolas
AU - Dirks, Ron P.
AU - O’connor, Sarah Ellen
AU - Jensen, Michael Krogh
AU - Besseau, Sébastien
AU - Courdavault, Vincent
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
U2 - 10.1038/s42003-023-05574-8
DO - 10.1038/s42003-023-05574-8
M3 - Journal article
C2 - 38001233
AN - SCOPUS:85177746324
SN - 2399-3642
VL - 6
JO - Communications Biology
JF - Communications Biology
M1 - 1197
ER -