Fatty acid synthase I (Mycobacterium tuberculosis) (FAS-I)

Fatty acid synthase I (FAS-I) is a massive, multifunctional enzyme complex in Mycobacterium tuberculosis (Mtb) that is essential for the de novo synthesis of fatty acids (UniProt: P9WGR1). Unlike most bacteria that utilize a Type II fatty acid synthase system (FAS-II), mycobacteria uniquely employ both FAS-I and FAS-II systems; FAS-I produces the C16 and C26 fatty acid precursors that are subsequently elongated by FAS-II to form mycolic acids (PubMed: 10948178). These mycolic acids are critical components of the mycobacterial cell wall, providing a robust permeability barrier and contributing to the organism's virulence and antibiotic resistance (PubMed: 22933061). FAS-I is a validated therapeutic target, most notably for the frontline anti-tuberculosis drug pyrazinamide, which is converted into pyrazinoic acid to inhibit the enzyme's activity (Science: 289(5483)). Inhibition of FAS-I disrupts cell wall integrity and is particularly effective against non-replicating or slowly-growing bacilli, making it vital for shortening the duration of tuberculosis treatment (PubMed: 24511156).

Other names

FAS IFASIMultifunctional fatty acid synthaseFasRv2524c

Inhibition of de novo fatty acid synthesis by binding to the enzyme complex, thereby preventing the formation of C16 and C26 fatty acid precursors required for mycolic acid production (Science: 289(5483)).