Fatty acid synthase I (mycobacterial) (FAS I)

Fatty acid synthase I (FAS I) in mycobacteria is a large, multi-functional, homohexameric enzyme complex (~2 MDa) responsible for the de novo biosynthesis of long-chain fatty acids—critical precursors for mycolic acids, which constitute a major structural component of the mycobacterial cell envelope[1][3][5][7]. The enzyme has seven catalytic domains per subunit and is architecturally distinct from both mammalian and fungal FAS systems. This complex is essential for viability and virulence of Mycobacterium tuberculosis, making it a high-priority therapeutic target for tuberculosis drug discovery. Inhibiting FAS I blocks mycolic acid synthesis, leading to compromised cell wall integrity and loss of infectivity. The unique structure of mycobacterial FAS I enables selective inhibition by small molecules, providing an important avenue for anti-tubercular drug development[1][5][7].

Other names

FAS IType I fatty acid synthaseMycobacterial fatty acid synthase IMultienzyme fatty acid synthase complex

Inhibitors block fatty acid chain elongation by binding to catalytic domains (e.g., ketoacyl synthase) in FAS I[5]. Result in disruption of mycolic acid biosynthesis, weakening or killing mycobacteria[1][5]