The primary step of biotin synthesis in mycobacteria
Zhe Hu, John E. Cronan
Abstract
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.