Mycobacterial fatty acid and mycolate biosynthesis pathway (FAS/MA pathway)

The mycobacterial fatty acid and mycolate biosynthesis pathway is an essential metabolic process responsible for producing mycolic acids, which are the primary lipid components of the mycobacterial cell wall [1.1.1, 1.3.1]. This pathway involves the coordinated action of two distinct systems: Fatty Acid Synthase I (FAS-I), which performs de novo synthesis of short-chain fatty acids, and Fatty Acid Synthase II (FAS-II), which elongates these precursors into the very long-chain meromycolate backbone [1.1.2, 1.3.3]. Mycolic acids form a dense, impermeable barrier that protects the bacteria from host immune defenses and many antibiotics, contributing significantly to the virulence and intrinsic resistance of pathogens like Mycobacterium tuberculosis [1.2.1, 1.3.4]. The pathway is the target of several critical anti-tuberculosis drugs, including isoniazid and ethionamide, which inhibit the enoyl-ACP reductase (InhA) enzyme within the FAS-II system [1.3.1, 1.4.1]. Disruption of these biosynthetic steps leads to the loss of cell wall integrity, resulting in bacterial lysis and death [1.3.3, 1.4.3]. Consequently, this pathway remains a focal point for the development of novel therapeutics to combat multi-drug resistant tuberculosis [1.4.4].

Other names

Mycolic acid biosynthesis pathwayMycobacterial FAS-I/FAS-II pathwayMycobacterial cell wall lipid synthesis pathway

Inhibition of key enzymes including enoyl-ACP reductase (InhA), beta-ketoacyl-ACP synthase (KasA/KasB), fatty acid synthase I (FAS-I), and the dehydratase complex (HadABC), as well as the transport of mycolic acids via MmpL3 [1.3.1, 1.4.1, 1.4.3].