| Description: | The MEP pathway is used by most bacteria, including all Gram-negative bacteria, for isoprenoid biosynthesis. Isoprenoids comprise one of the most diverse classes of compounds found in nature. With over 50,000 different isoprenoids identified to date, they exhibit a broad range of structural complexity and are involved in a variety of biological functions [1] including Electron transport (quinones), stabilization of cell membranes (hopanoids and sterols), cell wall biosynthesis (dolichols), signal transduction (prenylated proteins), photosynthesis (chlorophylls) and modification of tRNAs. [2] Isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) are the precursors for all isoprenoid compounds and the MEP pathway is one of two unrelated essential pathways existing in nature for their biosynthesis. These two precursors are produced by either the mevalonate (MVA) or MEP pathway. The MVA pathway is found primarily in eukaryotes, including humans, plant cytosol, Archaea, and some Gram-positive bacteria, while the MEP pathway is utilized by most bacteria and plant chloroplasts. Due to this natural distribution, the MEP pathway represents a promising target for development of novel antibacterial agents and herbicides. In the first pathway-specific reaction of the methylerythritol phosphate (MEP) pathway for isoprenoid biosynthesis, MEP Synthase (DXR) catalyzes the rearrangement of 1-deoxy-D-xylulose-5-phosphate (DXP) to generate 2-C-methyl-D-erythritol-4-phosphate (MEP) in the presence of ?-nicotinamide adenine dinucleotide phosphate (NADPH) and a divalent cation. [4] Fosmidomycin is a natural product inhibitor of MEP synthase and has validated the MEP pathway as an antibiotic target. |
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