Fatty acid synthase 1 (Mycobacterium tuberculosis) (FAS-I)

Mycobacterium tuberculosis Fatty Acid Synthase 1 (FAS-I) is a massive, multifunctional enzyme complex (encoded by Rv2524c) that catalyzes the de novo synthesis of C16–C26 fatty acids, which serve as essential precursors for mycolic acid production (Zimhony et al., 2000; UniProt P9WGR1). This enzyme is a primary target of the frontline anti-tuberculosis drug Pyrazinamide, which is converted into pyrazinoic acid to inhibit FAS-I and disrupt the mycobacterial cell wall (Zimhony et al., 2000). The target description also encompasses related energy metabolism pathways, such as the mycobacterial ATP synthase (targeted by Bedaquiline) and the cytochrome bc1-aa3 complex (targeted by Telacebec), which are critical for maintaining the proton motive force and cellular ATP levels in both active and dormant states (Cook et al., 2017; Pethe et al., 2013). Together, these fatty acid and energy metabolism targets represent a vital metabolic axis for Mtb survival and are central to modern multi-drug resistant tuberculosis (MDR-TB) treatment strategies (Nataraj et al., 2015).

Other names

FAS1Multifunctional fatty acid synthaseType I fatty acid synthaseRv2524cATP synthaseCytochrome bc1-aa3 complex

Inhibition of de novo fatty acid synthesis by FAS-I and disruption of oxidative phosphorylation via ATP synthase or the cytochrome bc1-aa3 complex (Zimhony et al., 2000; Cook et al., 2017).