Fatty acid synthase systems (FAS-I and FAS-II) involved in mycolic acid synthesis (FAS-I/FAS-II)

The fatty acid synthase (FAS) systems in Mycobacterium tuberculosis are essential for the production of mycolic acids, which are long-chain fatty acids (C60-C90) that form the core of the mycobacterial cell wall (1.3.1, 1.3.5). This pathway consists of two distinct systems: FAS-I, a single multifunctional enzyme that performs de novo synthesis of C16-C26 fatty acids, and FAS-II, a complex of dissociated enzymes (including InhA, KasA, KasB, and HadABC) that elongates these precursors into long meromycolic chains (1.3.3, 1.4.4). These systems are critical for bacterial survival, virulence, and resistance to environmental stress, as the resulting mycolic acids provide a formidable permeability barrier (1.2.4, 1.3.4). Several frontline antitubercular drugs, such as isoniazid and pyrazinamide, exert their effects by inhibiting specific components of these systems, such as the enoyl-ACP reductase InhA or the FAS-I enzyme itself (1.2.2, 1.5.2). Disrupting this pathway weakens the cell wall, making the bacteria more susceptible to other drugs and host immune responses (1.2.4, 1.5.1). Furthermore, the unique nature of the FAS-II system, which is absent in humans, makes it an ideal target for the development of selective antimicrobial agents with minimal off-target effects (1.5.1, 1.5.3).

Other names

Mycobacterial fatty acid synthase systemsFAS-I and FAS-II pathwaysMycolic acid biosynthetic pathwayType I and Type II fatty acid synthases

Inhibition of the fatty acid synthase I (FAS-I) and fatty acid synthase II (FAS-II) systems, which are responsible for the de novo synthesis and elongation of fatty acids into mycolic acids, essential components of the mycobacterial cell wall (1.2.2, 1.3.1).