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Adenosylcobinamide-GDP ribazoletransferase, commonly known as Cobalamin synthase or CobS, is a critical enzyme in the biosynthetic pathway of Vitamin B12 (cobalamin) in bacteria and archaea [4, 5]. It catalyzes the final step of the pathway: the condensation of adenosylcobinamide-GDP with alpha-ribazole to form adenosylcobalamin [2, 6]. This enzyme is essential for microorganisms that rely on de novo B12 synthesis for vital processes such as DNA synthesis and amino acid metabolism [13, 17]. Because humans lack the entire cobalamin biosynthetic machinery and must obtain the vitamin from their diet, CobS represents a promising target for the development of novel, selective antibacterial agents [14, 20]. Inhibition of this enzyme would disrupt B12 production in pathogens like Mycobacterium tuberculosis, potentially leading to bacterial growth inhibition without affecting human host cells [13, 14]. While no clinical drugs currently target CobS, it remains a focal point in research aimed at overcoming antimicrobial resistance by targeting unique bacterial metabolic pathways [19, 21].
Inhibition of cobalamin biosynthesis
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