Methylerythritol phosphate pathway (MEP pathway)

The methylerythritol phosphate (MEP) pathway is a critical seven-step metabolic route used by various bacteria, plants, and apicomplexan parasites like Plasmodium to produce essential isoprenoids [1, 7]. These compounds are vital building blocks for fundamental cellular components, including cell walls (peptidoglycan precursors), respiratory molecules (menaquinone), and photosynthetic pigments in plants [4, 9]. Unlike humans and other mammals, who rely on the mevalonate (MVA) pathway for isoprenoid biosynthesis, many significant pathogens utilize the MEP pathway exclusively [1, 5]. This fundamental metabolic difference, known as orthogonality, creates a unique therapeutic window for selective antimicrobial and antimalarial drugs that exhibit low toxicity toward human cells [3, 8]. Drugs like fosmidomycin target specific enzymes within this pathway, such as 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR), to halt the synthesis of life-sustaining precursors [4, 6]. Ongoing research aims to identify inhibitors for other enzymes in the pathway, including DXS and IspF, to develop next-generation anti-infectives capable of overcoming current drug resistance [4, 12, 13].

Other names

Non-mevalonate pathway1-deoxy-D-xylulose 5-phosphate pathwayDXP pathwayDOXP pathwayRohmer pathwayMevalonate-independent pathway2-C-methyl-D-erythritol 4-phosphate pathway

Specific inhibition of individual enzymes such as 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR/IspC) and 1-deoxy-D-xylulose 5-phosphate synthase (DXS); General disruption of the non-mevalonate route for isoprenoid precursor biosynthesis [1, 4, 12].