Mycobacterium tuberculosis fatty acid synthase I (FAS I)

Mycobacterium tuberculosis fatty acid synthase I (FAS I) is a large (~1.9–2 MDa) homohexameric, multi-functional, multi-domain enzymatic complex essential for the survival and virulence of the bacterium[1][2][7]. Unlike most prokaryotes, M. tuberculosis utilizes a structurally integrated type I fatty acid synthase rather than the usual type II system for de novo long-chain fatty acid synthesis[5]. FAS I is responsible for the initial synthesis of fatty acids (up to C16–C26), which act as precursors for cell wall components such as mycolic acids. The FAS I system requires activation by covalent attachment of 4'-phosphopantetheine (P-pant) to its ACP domain, a process catalyzed by acyl carrier protein synthase (AcpS)[1][4]. Active FAS I is critical for drug binding and inhibition studies, as it is a promising target for anti-tubercular drugs, particularly pyrazinamide and its analogs, which act by competitive inhibition of FAS I catalytic activity[6][7]. This molecule is a validated therapeutic target in tuberculosis drug discovery and continues to be central for the development of drugs active against multidrug-resistant M. tuberculosis strains[2][7].

Other names

Mtb FAS-IType-I fatty acid synthaseFatty acid synthase 1 of Mycobacterium tuberculosis

Competitive inhibition of FAS I enzymatic activity Direct binding and inhibition by pyrazinamide and analogs[6]