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Enzymatic Synthesis of Epoxidized Metabolites of Docosahexaenoic, Eicosapentaenoic, and Arachidonic Acids
Published on: June 28, 2019
IspG converts an epoxide substrate analogue to (E)-4-hydroxy-3-methylbut-2-enyl diphosphate: implications for IspG
Rodney L Nyland1, Youli Xiao, Pinghua Liu
1Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
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.
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