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

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.

SUBMITTER: Dang TT 

PROVIDER: S-EPMC5582599 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature