Mycobacterial enzymes

Mycobacterial enzymes constitute a broad class of catalytic proteins essential for the survival, pathogenesis, and structural integrity of Mycobacterium species, particularly Mycobacterium tuberculosis (Mtb). These enzymes serve as the primary molecular targets for nearly all established antitubercular therapies, which disrupt vital bacterial processes such as mycolic acid biosynthesis (e.g., InhA), RNA transcription (e.g., RpoB), and energy production (e.g., ATP synthase) [1, 6, 7]. The unique and complex nature of the mycobacterial cell envelope, characterized by a thick layer of mycolic acids and arabinogalactan, relies on specialized enzymes like DprE1 and Pks13, which are absent in humans and thus provide high selectivity for drug development [5, 11, 15]. However, the ability of these enzymes to undergo mutational changes leads to the emergence of multi-drug resistant (MDR) and extensively drug-resistant (XDR) strains, necessitating the continuous identification of novel enzymatic targets [7, 13]. Furthermore, some mycobacterial enzymes, such as KatG, are required to activate prodrugs like isoniazid, making their functional status a critical determinant of drug efficacy [6, 8].

Other names

Mtb enzymesMycobacterium tuberculosis enzymesAntitubercular enzyme targetsMycobacterial drug targets

Inhibition of essential bacterial metabolic and structural pathways, including the synthesis of mycolic acids (InhA), arabinogalactan (EmbB), and peptidoglycan, as well as the disruption of nucleic acid synthesis (RpoB, DNA gyrase) and ATP generation (ATP synthase) [5, 6, 11].