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As multidrug resistant pathogenic microorganisms are a serious health menace, it is crucial to continuously develop novel medicines in order to overcome the emerging resistance. The methylerythritol phosphate pathway (MEP) is an ideal target for antimicrobial development as it is absent in humans but present in most bacteria and in the parasite  Plasmodium falciparum . Here, we report the synthesis and the steady-state kinetics of a novel potent inhibitor (MEPN 3 ) of  Escherichia coli  YgbP/IspD, the third enzyme of the MEP pathway. MEPN 3  inhibits  E .  coli  YgbP/IspD in mixed type mode regarding both substrates. Interestingly, MEPN 3  shows the highest inhibitory activity when compared to known inhibitors of  E .  coli  YgbP/IspD. The mechanism of this enzyme was also studied by steady-state kinetic analysis and it was found that the substrates add to the enzyme in sequential manner.

Synthesis and Kinetic evaluation of an azido analogue of methylerythritol phosphate: a Novel Inhibitor of E. coli YgbP/IspD