Mycolic acid biosynthetic pathway enzymes (MBS)

Mycolic acid synthesis enzymes in Mycobacterium tuberculosis represent a critical group of therapeutic targets responsible for producing the long-chain fatty acids that constitute the hallmark waxy cell wall of the bacterium. This pathway involves two distinct systems: Fatty Acid Synthase I (FAS-I), which produces short-chain fatty acids, and Fatty Acid Synthase II (FAS-II), which elongates them into the precursors of mycolic acids. Key enzymes within this pathway, such as the enoyl-ACP reductase (InhA) and the beta-ketoacyl-ACP synthase (KasA), are the primary targets for frontline antitubercular drugs like isoniazid. By inhibiting these enzymes, drugs disrupt the integrity of the mycobacterial cell envelope, making the pathogen susceptible to host immune responses and other antibiotics. Given that mycolic acids are unique to mycobacteria and essential for their survival and virulence, these enzymes remain a focal point for the development of new treatments against multi-drug resistant tuberculosis strains.

Other names

Mycolic acid synthesis enzymesFatty acid synthase II systemFAS-II complexMycolic acid biosynthesis pathway

Inhibition of various enzymes within the FAS-II system (e.g., InhA, KasA) or the condensation step (Pks13), leading to the depletion of mycolic acids, which are essential components of the mycobacterial cell wall, ultimately causing cell lysis and death.