Isoprenoid biosynthesis via the mevalonate-independent route, a novel target for antibacterial drugs?

Abstract

Mevalonate was accepted as the universal precursor of all isoprenoids. This assertion was however revealed to be partially incorrect. Incorporation of 13C labeled acetate and glucose into bacterial triterpenoids of the hopane series allowed for the discovery and the partial elucidation of a novel biosynthetic pathway leading to isopentenyl diphosphate. The Cs skeleton of isoprenic units results from the condensation of (hydroxyethyl)thiamin on the carbonyl group of glyceraldehyde 3-phosphate, yielding D-1-deoxyxylulose 1-phosphate. A subsequent intramolecular rearrangement is involved in the formation of the branched isoprenic skeleton. 2C-Methyl-D-erythritol (or its mono- or diphosphate) was shown to be a putative intermediate. This pathway is widespread in bacteria including opportunistic pathogens or innocuous species related to well-known pathogens. In plants, it is involved in the formation of essential chloroplast isoprenoids (carotenoids, phytol, plastoquinone) and of probably most other plastid related isoprenoids of more restricted distribution (isoprene, mono- and diterpenoids). Therefore it potentially represents a novel target for antibacterial drugs and herbicides.