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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / biosynthesis*
  • Alkaloids / chemistry
  • Biocatalysis
  • Cytochrome P-450 Enzyme System / metabolism*
  • Molecular Conformation
  • Rauwolfia / chemistry*
  • Rauwolfia / metabolism


  • Alkaloids
  • Cytochrome P-450 Enzyme System