2-C-methyl-D-erythritol 4-phosphate
Introduction
2-C-methyl-D-erythritol 4-phosphate (MEP) is an intermediate in the non-mevalonate pathway of isoprenoid biosynthesis. This pathway is also known as the 2-C-methyl-D-erythritol 4-phosphate/1-deoxy-D-xylulose 5-phosphate (MEP/DOXP) pathway. The MEP pathway is present in most bacteria, some eukaryotic parasites, and the plastids of plants. It is absent in animals, fungi, and archaea, which instead use the mevalonate pathway for isoprenoid biosynthesis.
Biosynthesis
The biosynthesis of MEP begins with the condensation of pyruvate and glyceraldehyde 3-phosphate, catalyzed by the enzyme 1-deoxy-D-xylulose-5-phosphate synthase (DXS). The resulting product, 1-deoxy-D-xylulose 5-phosphate (DOXP), is then reduced by the enzyme DOXP reductoisomerase (DXR) to produce MEP.
Role in Isoprenoid Biosynthesis
MEP is a critical intermediate in the biosynthesis of isoprenoids, a large and diverse class of metabolites that includes essential molecules such as quinones, terpenes, and carotenoids. From MEP, the pathway proceeds through a series of enzymatic reactions to produce the five-carbon isoprenoid building blocks, isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP).
Enzymatic Reactions Involving MEP
MEP is involved in several enzymatic reactions in the MEP pathway. These reactions are catalyzed by a series of enzymes, including MEP cytidylyltransferase, 4-diphosphocytidyl-2-C-methyl-D-erythritol kinase, 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase, and hydroxymethylbutenyl diphosphate synthase (HDS). The final product of these reactions is HMBPP, which is then converted to IPP and DMAPP by HDS and hydroxymethylbutenyl diphosphate reductase (HDR).
Significance in Drug Discovery
The MEP pathway, and by extension MEP itself, has been the focus of significant interest in drug discovery due to its presence in many pathogenic organisms and its absence in humans. Inhibitors of the enzymes in the MEP pathway, particularly DXR, have been explored as potential antimicrobial and antiparasitic agents.