Nicotinate-nucleotide—dimethylbenzimidazole phosphoribosyltransferase (CobT)

Nicotinate-nucleotide—dimethylbenzimidazole phosphoribosyltransferase, commonly known as CobT, is a critical enzyme in the aerobic and anaerobic biosynthesis of cobalamin (Vitamin B12) in various bacteria and archaea. It catalyzes the reaction between nicotinate mononucleotide (NaMN) and 5,6-dimethylbenzimidazole (DMB) to form alpha-ribazole-5'-phosphate, a precursor required for the final assembly of the B12 molecule (UniProt P29933). Because humans and other mammals lack the machinery to synthesize Vitamin B12 de novo and must obtain it through diet, CobT represents a potential selective target for the development of narrow-spectrum antibacterial agents (PubMed: 10490589). Inhibiting this enzyme can starve pathogenic bacteria of an essential cofactor required for DNA synthesis and metabolic reactions. While research has explored various DMB analogs as potential inhibitors, there are currently no FDA-approved drugs that specifically target CobT. The enzyme's role is particularly significant in pathogens that rely on endogenous B12 production for survival within the host environment (PubMed: 11790105).

Other names

CobTDimethylbenzimidazole phosphoribosyltransferaseNaMN:5,6-dimethylbenzimidazole phosphoribosyltransferaseNicotinate-nucleotide:dimethylbenzimidazole phosphoribosyltransferase

Inhibition of the CobT enzyme disrupts the late stages of the cobalamin (Vitamin B12) biosynthetic pathway, preventing the formation of the lower ligand alpha-ribazole, which is essential for the assembly of the complete B12 cofactor in bacteria.