Enzymes of mycolic acid synthesis

Enzymes of mycolic acid synthesis are essential for the production of the unique, long-chain fatty acids that constitute the mycobacterial cell wall, providing a robust barrier against environmental stress and antibiotics (Marrakchi et al., 2014, PMID: 24433161). This pathway involves the Fatty Acid Synthase II (FAS-II) system, which elongates fatty acid precursors into meromycolic acids, and the final condensation step mediated by Polyketide Synthase 13 (Pks13) (North et al., 2014, PMID: 24509461). Key enzymes such as enoyl-ACP reductase (InhA) and beta-ketoacyl-ACP synthases (KasA/B) are critical for maintaining cell envelope integrity (Vilchèze & Jacobs, 2007, PMID: 17634103). Drugs like isoniazid and ethionamide target InhA, leading to the inhibition of mycolic acid synthesis and subsequent bacterial lysis (StatPearls, 2023, NBK531492). Because these enzymes are specific to mycobacteria and lack human homologs, they are primary targets for anti-tuberculosis drug development, although resistance mutations in genes like inhA and katG pose significant therapeutic challenges (UniProt, P9WGR1). Other drugs like delamanid and pretomanid also interfere with this pathway, specifically affecting the synthesis of methoxy- and keto-mycolic acids (Manjunatha et al., 2009, PMID: 19033437). Overall, this enzymatic complex is a cornerstone of modern mycobacterial therapy.

Other names

Mycolic acid biosynthetic pathwayFAS-II system enzymesMycolic acid assembly machineryMABAMycolic acid synthase

Inhibition of various stages of mycolic acid biosynthesis, including the elongation of fatty acids by the FAS-II system (e.g., InhA inhibition) and the final condensation of meromycolate chains (e.g., Pks13 inhibition), leading to cell wall disruption (Vilchèze & Jacobs, 2007; North et al., 2014).