Vitamin B12 biosynthetic enzymes

Vitamin B12 biosynthetic enzymes are a group of approximately 30 proteins that catalyze the complex de novo synthesis of cobalamin, a process found exclusively in certain bacteria and archaea (Warren et al., 2002). Humans and other eukaryotes lack these enzymes and must obtain Vitamin B12 through dietary sources, making this pathway an attractive target for narrow-spectrum antimicrobial development (Moore et al., 2014). The pathway is divided into two main routes: the aerobic (oxygen-dependent) and anaerobic (oxygen-independent) pathways, which differ primarily in the timing of cobalt insertion and the requirement for molecular oxygen (Martens et al., 2002). Key enzymes in these pathways, such as cobaltochelatases (e.g., CbiK, CobNST) and adenosyltransferases (e.g., CobA), are essential for pathogens like Mycobacterium tuberculosis and Salmonella enterica to maintain metabolic functions including DNA synthesis and methionine production (Deery et al., 2012). Inhibiting these enzymes offers a strategy to treat infections by starving the pathogen of a vital cofactor while minimizing direct toxicity to the human host, who lacks the target enzymes entirely (Raux et al., 2000). However, therapeutic challenges include the potential for pathogens to scavenge B12 from the host environment and the risk of altering the host's commensal microbiota (Fang et al., 2017).

Other names

Cobalamin biosynthetic enzymesCorrinoid biosynthetic enzymesVitamin B12 synthesis pathway enzymesCbi/Cob enzymes

Inhibition of specific enzymes within the de novo cobalamin biosynthetic pathway to prevent the production of essential Vitamin B12 cofactors in pathogenic bacteria, leading to metabolic arrest and growth inhibition.