Menaquinone is the sole quinone in the mycobacterial electron transport chain and, since the pathway leading to the biosynthesis of menaquinone is absent in humans, the bacterial enzymes catalyzing the synthesis of menaquinone from chorismate are potential novel targets for drug discovery. Since latent MTB must presumably respire at some low rate in order to remain viable, compounds that target respiration have the potential to be active against non-replicating MTB. The biosynthesis of menaquinone has been extensively studied in E. coli and B. subtilis. Homologs of all but one of the E. coil enzymes are present in M. tuberculosis. We are currently studying MenB and MenE from MTB and are seeking to identify the menaquinone-specific isochorismate synthase (MenF) in MTB. We have solved the structures of MenB and the E. coli MenF as well as MbtI, the salicylate synthase from the mycobactin biosynthetic operon. |
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