Catalase-peroxidase (KatG)

Catalase-peroxidase, commonly known as KatG, is a bifunctional heme-containing enzyme primarily found in Mycobacterium tuberculosis and other bacteria [1, 2]. It possesses both catalase activity, which decomposes hydrogen peroxide into water and oxygen, and peroxidase activity, which uses various electron donors to reduce peroxides [2, 3]. In the context of tuberculosis treatment, KatG is the essential activator of the first-line prodrug isoniazid [1, 6]. It catalyzes the oxidative conversion of isoniazid into an isonicotinoyl radical, which subsequently forms a covalent adduct with NAD+ [4, 6]. This adduct then inhibits InhA, an enzyme critical for mycolic acid biosynthesis and cell wall integrity [6, 7]. Mutations in the katG gene, most notably the S315T substitution, are the primary cause of high-level isoniazid resistance in clinical settings, as they impair the enzyme's ability to activate the drug while often preserving enough catalase activity for bacterial survival and virulence [13, 16, 19].

Other names

KatGHPIHydroperoxidase ICatalase-peroxidase 1

Oxidative activation of the prodrug isoniazid into an isonicotinoyl-NAD adduct that inhibits enoyl-acyl carrier protein reductase (InhA), thereby blocking mycolic acid synthesis.