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

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The Rauvolfia tetraphylla genome suggests multiple distinct biosynthetic routes for yohimbane monoterpene indole alkaloids. / Stander, Emily Amor; Lehka, Beata; Carqueijeiro, Inês; Cuello, Clément; Hansson, Frederik G.; Jansen, Hans J.; Dugé De Bernonville, Thomas; Birer Williams, Caroline; Vergès, Valentin; Lezin, Enzo; Lorensen, Marcus Daniel Brandbjerg Bohn; Dang, Thu Thuy; Oudin, Audrey; Lanoue, Arnaud; Durand, Mickael; Giglioli-Guivarc’h, Nathalie; Janfelt, Christian; Papon, Nicolas; Dirks, Ron P.; O’connor, Sarah Ellen; Jensen, Michael Krogh; Besseau, Sébastien; Courdavault, Vincent.

In: Communications Biology , Vol. 6, No. 1, 1197, 2023.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

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 2023, 'The Rauvolfia tetraphylla genome suggests multiple distinct biosynthetic routes for yohimbane monoterpene indole alkaloids', Communications Biology , vol. 6, no. 1, 1197. https://doi.org/10.1038/s42003-023-05574-8

APA

Stander, E. A., Lehka, B., Carqueijeiro, I., Cuello, C., Hansson, F. G., Jansen, H. J., Dugé De Bernonville, T., Birer Williams, C., Vergès, V., Lezin, E., Lorensen, M. D. B. B., Dang, T. T., Oudin, A., Lanoue, A., Durand, M., Giglioli-Guivarc’h, N., Janfelt, C., Papon, N., Dirks, R. P., ... Courdavault, V. (2023). The Rauvolfia tetraphylla genome suggests multiple distinct biosynthetic routes for yohimbane monoterpene indole alkaloids. Communications Biology , 6(1), [1197]. https://doi.org/10.1038/s42003-023-05574-8

Vancouver

Stander EA, Lehka B, Carqueijeiro I, Cuello C, Hansson FG, Jansen HJ et al. The Rauvolfia tetraphylla genome suggests multiple distinct biosynthetic routes for yohimbane monoterpene indole alkaloids. Communications Biology . 2023;6(1). 1197. https://doi.org/10.1038/s42003-023-05574-8

Author

Stander, Emily Amor ; Lehka, Beata ; Carqueijeiro, Inês ; Cuello, Clément ; Hansson, Frederik G. ; Jansen, Hans J. ; Dugé De Bernonville, Thomas ; Birer Williams, Caroline ; Vergès, Valentin ; Lezin, Enzo ; Lorensen, Marcus Daniel Brandbjerg Bohn ; Dang, Thu Thuy ; Oudin, Audrey ; Lanoue, Arnaud ; Durand, Mickael ; Giglioli-Guivarc’h, Nathalie ; Janfelt, Christian ; Papon, Nicolas ; Dirks, Ron P. ; O’connor, Sarah Ellen ; Jensen, Michael Krogh ; Besseau, Sébastien ; Courdavault, Vincent. / The Rauvolfia tetraphylla genome suggests multiple distinct biosynthetic routes for yohimbane monoterpene indole alkaloids. In: Communications Biology . 2023 ; Vol. 6, No. 1.

Bibtex

@article{9d4cc82700604e66b136fcad9dfc29d0,

title = "The Rauvolfia tetraphylla genome suggests multiple distinct biosynthetic routes for yohimbane monoterpene indole alkaloids",

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.",

author = "Stander, {Emily Amor} and Beata Lehka and In{\^e}s Carqueijeiro and Cl{\'e}ment Cuello and Hansson, {Frederik G.} and Jansen, {Hans J.} and {Dug{\'e} De Bernonville}, Thomas and {Birer Williams}, Caroline and Valentin Verg{\`e}s and Enzo Lezin and Lorensen, {Marcus Daniel Brandbjerg Bohn} and Dang, {Thu Thuy} and Audrey Oudin and Arnaud Lanoue and Mickael Durand and Nathalie Giglioli-Guivarc{\textquoteright}h and Christian Janfelt and Nicolas Papon and Dirks, {Ron P.} and O{\textquoteright}connor, {Sarah Ellen} and Jensen, {Michael Krogh} and S{\'e}bastien Besseau and Vincent Courdavault",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

doi = "10.1038/s42003-023-05574-8",

language = "English",

volume = "6",

journal = "Communications Biology",

issn = "2399-3642",

publisher = "nature publishing group",

number = "1",

}

RIS

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

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

VL - 6

JO - Communications Biology

JF - Communications Biology

SN - 2399-3642

IS - 1

M1 - 1197

ER -

ID: 375208209

Department of Pharmacy