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. Author manuscript; available in PMC: 2016 May 15.
Published in final edited form as: J Org Chem. 2015 Apr 30;80(10):4835–4850. doi: 10.1021/acs.joc.5b00550

Figure 2.

Figure 2

Mycobactin biosynthesis and inhibition. (A) The biosynthesis of mycobactins in M. tuberculosis is initiated by MbtA that catalyzes two partial reactions at the same active site. In the first half-reaction MbtA condenses salicylic acid (7) with ATP to form the reactive mixed anhydride SAL-AMP (8). In the second half-reaction MbtA transfers the salicyl moiety onto MbtB, another protein in the biochemical pathway, to afford 9 that is ultimately elaborated to the mycobactins. The initial biosynthetic step of other aryl-capped siderophores is performed by homologous aryl acid adenylation enzymes (AAAEs). (B) The inhibitors Sal-AMS 10 and its sulfamide isostere 11 mimic the acyl-adenylate intermediate 8, thereby blocking siderophore biosynthesis. The sugar can adopt the Northern (C3′-endo pucker) or Southern (C2′-endo pucker) conformation as depicted. (C) Fluorinated sugar analogs described in this study.