Fatty acid synthase II system (FAS-II) (FAS-II)

The Fatty Acid Synthase II (FAS-II) system is a multi-enzyme complex in Mycobacterium tuberculosis responsible for the synthesis of long-chain mycolic acids (C50-C90), which are critical components of the mycobacterial cell wall (Marrakchi et al., 2000, PMID: 10986241). Unlike the single-polypeptide FAS-I system found in eukaryotes, FAS-II consists of several discrete enzymes, including InhA (enoyl-ACP reductase), KasA/KasB (beta-ketoacyl-ACP synthases), and the HadABC complex (dehydratases), making it a highly specific target for anti-tubercular therapy (Cantrell et al., 2013, PMID: 23603771). Mycolic acids provide a thick, waxy barrier that protects the bacterium from host immune responses and antibiotic penetration (Nikaido, 2003, PMID: 12624051). Drugs like isoniazid and ethionamide are pro-drugs that, once activated, target the InhA component of this complex, disrupting cell wall integrity and leading to bacterial lysis (Vilchèze & Jacobs, 2007, PMID: 17569937). Because the FAS-II architecture is distinct from human fatty acid synthesis, it offers a high therapeutic index, though resistance through mutations in target enzymes like InhA remains a significant clinical challenge in treating tuberculosis (Unissa et al., 2016, PMID: 27507144).

Other names

Mycolic acid synthesis enzyme complexFAS-II complexFatty acid synthase IIInhA-containing complexMycolic acid biosynthesis pathway

Inhibition of specific enzymes within the FAS-II complex, primarily InhA (enoyl-ACP reductase), which prevents the elongation of fatty acids into long-chain mycolic acids, resulting in the loss of cell wall integrity and bacterial death (Vilchèze & Jacobs, 2007, PMID: 17569937).