Mycobacterium tuberculosis type II fatty acid synthase system (FAS-II)

The Mycobacterium tuberculosis type II fatty acid synthase (FAS-II) system is a collection of discrete enzymes that work coordinately to elongate fatty acids into long-chain (C60-C90) mycolic acids. These mycolic acids are vital structural components of the mycobacterial cell envelope, providing a hydrophobic barrier that contributes to the pathogen's resilience and antibiotic resistance (PMID: 21859251). The FAS-II system is distinct from the human FAS-I system, which utilizes a single multifunctional polypeptide, making FAS-II a highly selective target for antimicrobial therapy (PMID: 15659395). Key enzymes within this system include the enoyl-ACP reductase InhA, the beta-ketoacyl-ACP synthases KasA and KasB, and the dehydratase complex HadABC. Clinically significant drugs like isoniazid and ethionamide are prodrugs that, upon activation, target the InhA enzyme to halt the production of mycolic acids (UniProt: P9WGR1). Disruption of this pathway leads to the loss of acid-fastness and eventual cell death due to the compromised integrity of the protective cell wall. Because of its essentiality for survival and virulence, the FAS-II pathway is a primary focus for the development of new treatments against multidrug-resistant tuberculosis (MDR-TB).

Other names

Fatty acid synthase IIFAS-II complexMycolic acid biosynthesis pathwayType II fatty acid synthase

Inhibition of enoyl-acyl carrier protein reductase (InhA), inhibition of beta-ketoacyl-ACP synthases (KasA/B), and inhibition of beta-hydroxyacyl-ACP dehydratase (HadABC) to disrupt mycolic acid synthesis.