Mycobacterium tuberculosis mycolic acid synthesis pathway (Mtb MAS pathway)

The Mycobacterium tuberculosis mycolic acid synthesis pathway is a complex metabolic network essential for the production of mycolic acids, which are long-chain (C60-C90) alpha-branched, beta-hydroxylated fatty acids that form the primary structural component of the mycobacterial cell envelope (PMID: 21111014). This pathway is divided into two systems: Fatty Acid Synthase I (FAS-I), which synthesizes short-chain fatty acids, and Fatty Acid Synthase II (FAS-II), which extends these chains into the long meromycolate precursors (PMID: 15659714). These lipids create a hydrophobic barrier that protects the bacterium from environmental stress, host immune defenses, and many standard antibiotics. Several frontline and second-line antitubercular drugs, such as isoniazid and ethionamide, specifically target enzymes within this pathway, most notably the enoyl-ACP reductase InhA (PMID: 7915817). Inhibition of these enzymes leads to the depletion of mycolic acids, resulting in cell wall instability and bacterial lysis. Because this pathway is unique to mycobacteria and absent in humans, it remains a premier target for the development of narrow-spectrum antibiotics to treat both drug-sensitive and multi-drug-resistant tuberculosis (PMID: 31636123).

Other names

Mycolic acid biosynthesisFAS-II systemMycobacterial fatty acid synthesisMycolic acid metabolic pathway

Inhibition of key enzymes such as enoyl-ACP reductase (InhA) and beta-ketoacyl-ACP synthase (KasA/B) to disrupt the elongation of fatty acids required for mycolic acid production (PMID: 7915817, PMID: 15659714).