The primary step of biotin synthesis in mycobacteria

Significance Biotin is an enzyme cofactor required for growth of mycobacteria, and the Mycobacterium tuberculosis biotin synthetic pathway has become a validated target for antitubercular compounds. Current pathway lacks information on synthesis of the pimelate moiety that provides 7 of the 10 biotin carbon atoms. We report the first step in mycobacterial pimelate synthesis parallels the pathway first reported in Escherichia coli , in which BioC catalyzed O -methylation of a malonyl-acyl carrier protein primer allows entry into fatty acid synthesis. The mycobacterial Tam proteins functionally replace the E. coli BioC protein, although these proteins are annotated as performing a different function Moreover, tam gene function is required for biotin synthesis by Mycobacterium smegmatis and its transcription is repressed by exogenous biotin.