The deoxyxylulose phosphate pathway of isoprenoid biosynthesis. Discovery and function of the ispDEFGH genes and their cognate enzymes

Abstract

Isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) serve as the universal precursors for the biosynthesis of terpenes. Besides the well-known mevalonate pathway, a second biosynthetic pathway conducive to IPP and DMAPP via 1-deoxy-d-xylulose-5-phosphate and 2C-methyl-d-erythritol-4-phosphate has been discovered recently in plants and certain eubacteria. 2C-Methyl-d-erythritol-4-phosphate, the first committed intermediate of the deoxyxylulose phosphate pathway, is converted into 2C-methyl-d-erythritol 2,4-cyclodiphosphate by the catalytic action of three enzymes specified by the ispDEF genes. The cyclic diphosphate is reductively opened by the IspG protein affording 1-hydroxy-2-methyl-2-(E)-butenyl-4-diphosphate. This compound can be converted into IPP as well as DMAPP by the catalytic action of IspH protein. The enzymes of this pathway are potential targets for novel antibacterial, antimalarial, and herbicide agents.