IspG converts an epoxide substrate analogue to (E)-4-hydroxy-3-methylbut-2-enyl diphosphate: implications for IspG catalysis in isoprenoid biosynthesis

J Am Chem Soc. 2009 Dec 16;131(49):17734-5. doi: 10.1021/ja907470n.

Abstract

IspG is an intriguing enzyme in bacteria, parasite, and plant isoprenoid biosynthesis, and its catalytic mechanism remains elusive. We report here the synthesis of (2R,3R)-4-hydroxy-3-methyl-2,3-epoxybutanyl diphosphate (Epoxy-HMBPP), a proposed intermediate in one of the frequently cited mechanistic models. We have also demonstrated that this epoxide analogue is a catalytically competent IspG substrate. This study represents the first mechanistic study of this important enzyme.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alkyl and Aryl Transferases / metabolism*
  • Biocatalysis
  • Epoxy Compounds / chemistry
  • Epoxy Compounds / metabolism*
  • Organophosphorus Compounds / chemistry
  • Organophosphorus Compounds / metabolism*
  • Terpenes / chemistry
  • Terpenes / metabolism*

Substances

  • (E)-4-hydroxy-3-methylbut-2-enyl diphosphate
  • Epoxy Compounds
  • Organophosphorus Compounds
  • Terpenes
  • Alkyl and Aryl Transferases