Fatty acid synthase I (FAS-I) and Fatty acid synthase II (FAS-II) system (FAS-I (Fatty acid synthase I), FAS-II (Fatty acid synthase II))

Fatty acid synthase I (FAS-I) and fatty acid synthase II (FAS-II) represent two evolutionarily and chemically distinct multienzyme systems governing fatty acid biosynthesis in mycobacteria. FAS-I is a large, multifunctional polypeptide complex resembling eukaryotic fatty acid synthases, catalyzing the de novo synthesis of medium- to long-chain fatty acids from acetyl-CoA and malonyl-CoA. FAS-II is a system of discrete, acyl carrier protein-dependent enzymes analogous to those found in prokaryotes, responsible for elongating fatty acid chains produced by FAS-I into very-long-chain fatty acids, including mycolic acids that are integral to the mycobacterial cell wall. Both systems are indispensable for membrane function, cell envelope integrity, and pathogenicity, and are prime targets for anti-tuberculosis agents such as isoniazid and ethionamide, which disrupt mycolic acid biosynthesis and compromise cell wall formation. Targeting these systems presents therapeutic opportunities and challenges, including the risk of resistance and metabolic adaptation by the pathogen.

Other names

FAS-IFatty acid synthase IFAS-IIFatty acid synthase IIMycobacterial fatty acid synthase system

Inhibition of enoyl reductase or other condensing enzymes within FAS-II, halting mycolic acid synthesis and compromising cell wall formation; direct inhibition of FAS-I reduces fatty acid precursors required for cell wall biosynthesis; disruption of lipid homeostasis and envelope formation leading to cell death or increased drug sensitivity.