The MEP pathway and the development of inhibitors as potential anti-infective agents

The non-mevalonate (or MEP) pathway represents an essential biosynthetic route used by plants, algae, and eubacteria to generate isoprenoid precursors. The MEP pathway has also been genetically validated in pathogenic organisms such as P. falciparum and M. tuberculosis. As this pathway is absent in mammalian systems, the enzymes of the MEP pathway represent attractive targets for the development of novel herbicides and antimicrobial chemotherapeutics. This review examines the enzymes in the MEP pathway from a detailed medicinal chemistry and structural biology perspective. The binding modes of substrates and inhibitors are discussed, identifying key interactions that maybe exploitable in small molecule inhibitor design.