1-Deoxy-d-xylulose 5-phosphate reductoisomerase: an overview

The methylerythritol phosphate pathway to isoprenoids, an alternate biosynthetic route present in many bacteria, algae, plants, and the malarial parasite Plasmodium falciparum, has become an attractive target for the development of new antimalarial and antibacterial compounds. The second enzyme in this pathway, 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR; EC 1.1.1.267), has been shown to be the molecular target for fosmidomycin, a promising antimalarial drug. This enzyme converts 1-deoxy-d-xylulose 5-phosphate (DXP) into the branched compound 2-C-methyl-d-erythritol 4-phosphate (MEP). The transformation of DXP into MEP requires an isomerization, followed by a NADPH-dependent reduction. The discovery of DXR, its subsequent characterization, and the identification of inhibitors will be presented.