Mycolic acid synthesis machinery

The mycolic acid synthesis machinery is a specialized multi-enzyme system responsible for producing the unique, long-chain fatty acids that constitute the primary structural and protective component of the mycobacterial cell envelope [PubMed: 15769487]. This machinery is organized into two distinct systems: Fatty Acid Synthase I (FAS-I), which synthesizes short-chain fatty acids, and Fatty Acid Synthase II (FAS-II), which extends these into the long meromycolate chains required for cell wall integrity [UniProt: P9WGR1]. Key enzymes within this pathway, most notably the enoyl-ACP reductase InhA, are the primary targets for frontline antitubercular agents like isoniazid and ethionamide [PubMed: 25611365]. Beyond synthesis, the machinery includes the polyketide synthase Pks13 for final condensation and the MmpL3 transporter for moving mycolic acid precursors across the plasma membrane [PubMed: 22267511, PubMed: 23934154]. Because mycolic acids are essential for the survival, virulence, and intrinsic antibiotic resistance of Mycobacterium tuberculosis, this pathway is a cornerstone of modern tuberculosis therapy. Disruption of this machinery leads to the loss of acid-fastness, increased susceptibility to other drugs, and rapid bacterial lysis.

Other names

Mycolic acid biosynthetic pathwayFAS-II systemMycobacterial cell wall synthesis machineryFatty acid synthase II complex

Inhibition of various stages of mycolic acid production, including fatty acid elongation by the FAS-II complex (specifically InhA and KasA), final assembly by Pks13, and transmembrane transport of trehalose monomycolate by MmpL3.