The non-mevalonate pathway of isoprenoids: genes, enzymes and intermediates

Although the mevalonate pathway had been considered for a long time as the unique source of biosynthetic isoprenoids, an alternative pathway has recently been discovered. The first intermediate, 1-deoxy-D-xylulose 5-phosphate, is assembled by condensation of glyceraldehyde 3-phosphate and pyruvate. A skeletal rearrangement coupled with a reduction step affords the branched-chain polyol, 2C-methyl-D-erythritol 4-phosphate, which is subsequently converted into a cyclic 2,4-diphosphate by the consecutive action of three enzymes via nucleotide diphosphate intermediates. The genes specifying these enzymes have been cloned from bacteria, plants and protozoa. Their expression in recombinant bacterial hosts has opened the way to the identification of several novel pathway intermediates.