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Angew Chem Int Ed Engl. 2017 Aug 1;56(32):9440-9444. doi: 10.1002/anie.201705010. Epub 2017 Jul 12.

Dual Catalytic Activity of a Cytochrome P450 Controls Bifurcation at a Metabolic Branch Point of Alkaloid Biosynthesis in Rauwolfia serpentina.

Author information

1
Department of Biological Chemistry, John Innes Centre, Colney Lane, Norwich, UK.

Abstract

Plants create tremendous chemical diversity from a single biosynthetic intermediate. In plant-derived ajmalan alkaloid pathways, the biosynthetic intermediate vomilenine can be transformed into the anti-arrhythmic compound ajmaline, or alternatively, can isomerize to form perakine, an alkaloid with a structurally distinct scaffold. Here we report the discovery and characterization of vinorine hydroxylase, a cytochrome P450 enzyme that hydroxylates vinorine to form vomilenine, which was found to exist as a mixture of rapidly interconverting epimers. Surprisingly, this cytochrome P450 also catalyzes the non-oxidative isomerization of the ajmaline precursor vomilenine to perakine. This unusual dual catalytic activity of vinorine hydroxylase thereby provides a control mechanism for the bifurcation of these alkaloid pathway branches. This discovery highlights the unusual catalytic functionality that has evolved in plant pathways.

KEYWORDS:

alkaloids; biosynthesis; cytochrome p450s; perakine; vomilenine

PMID:
28654178
PMCID:
PMC5582599
DOI:
10.1002/anie.201705010
[Indexed for MEDLINE]
Free PMC Article

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