A Catharanthus roseus Fe(II)/α-ketoglutarate-dependent dioxygenase catalyzes a redox-neutral reaction responsible for vindolinine biosynthesis

Jasmine Ga May Eng, Mohammadamin Shahsavarani, Daniel Patrick Smith, Josef Hájíček, Vincenzo De Luca and Yang Qu ()
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Jasmine Ga May Eng: University of New Brunswick
Mohammadamin Shahsavarani: University of New Brunswick
Daniel Patrick Smith: University of New Brunswick
Josef Hájíček: Charles University in Prague
Vincenzo De Luca: Brock University
Yang Qu: University of New Brunswick

Nature Communications, 2022, vol. 13, issue 1, 1-9

Abstract: Abstract The Madagascar’s periwinkle is the model plant for studies of plant specialized metabolism and monoterpenoid indole alkaloids (MIAs), and an important source for the anticancer medicine vinblastine. The elucidation of entire 28-step biosynthesis of vinblastine allowed further investigations for the formation of other remarkably complex bioactive MIAs. In this study, we describe the discovery and characterization of vindolinine synthase, a Fe(II)/α-ketoglutarate-dependent (Fe/2OG) dioxygenase, that diverts assembly of tabersonine to vinblastine toward the formation of three alternatively cyclized MIAs: 19S-vindolinine, 19R-vindolinine, and venalstonine. Vindolinine synthase catalyzes a highly unusual, redox-neutral reaction to form a radical from dehydrosecodine, which is further cyclized by hydrolase 2 to form the three MIA isomers. We further show the biosynthesis of vindolinine epimers from tabersonine using hydrolase 2 catalyzed reverse cycloaddition. While the occurrence of vindolinines is rare in nature, the more widely found venalstonine derivatives are likely formed from similar redox-neutral reactions by homologous Fe/2OG dioxygenases.

Date: 2022
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DOI: 10.1038/s41467-022-31100-1

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