Mycobacterium tuberculosis mycolic acid biosynthesis pathway enzymes (Mtb FAS-II)

The Mycobacterium tuberculosis mycolic acid biosynthesis pathway enzymes are a critical group of proteins responsible for producing the unique, long-chain fatty acids that constitute the core of the mycobacterial cell envelope [Marrakchi et al., 2014]. This pathway is primarily organized into the Fatty Acid Synthase II (FAS-II) system, which elongates fatty acid precursors into long-chain mycolic acids (C60-C90) essential for bacterial survival [Takayama et al., 2005]. These lipids provide a formidable hydrophobic barrier that protects the pathogen from host immune responses and limits the penetration of many antibiotics [North et al., 2014]. Key enzymes within this pathway, most notably the enoyl-ACP reductase (InhA), serve as the primary targets for essential anti-tuberculosis drugs such as isoniazid and ethionamide [PubChem, CID 3767]. Inhibition of these enzymes disrupts cell wall assembly, leading to bacterial lysis and death [PubMed, PMID 15831413]. Because these enzymes are absent in humans, they represent highly specific and effective targets for therapeutic intervention against both active and drug-resistant tuberculosis [Drug Discov Today, 2014].

Other names

Mycolic acid biosynthesis pathwayFatty acid synthase II systemFAS-II complexM. tuberculosis cell wall synthesis enzymes

Inhibition of specific enzymes within the FAS-II system, such as enoyl-ACP reductase (InhA), beta-ketoacyl-ACP synthases (KasA/B), or dehydratases (HadABC), which prevents the elongation of fatty acids into essential mycolic acids [Takayama et al., 2005; PubMed, PMID 10940041].