Cobalamin biosynthesis pathway (B12 biosynthesis)

The cobalamin biosynthesis pathway is an intricate biochemical route responsible for the de novo synthesis of Vitamin B12, a vital cofactor for essential enzymes like methionine synthase and methylmalonyl-CoA mutase. This pathway is exclusive to specific prokaryotes (bacteria and archaea), as humans and other eukaryotes lack the genetic machinery required to synthesize the complex corrin ring structure and must obtain the vitamin through diet or symbiotic microbes [1][2]. Because many pathogens, including Mycobacterium tuberculosis, rely on this pathway for survival or pathogenesis, it represents a selective target for novel antimicrobial and antiparasitic drug development [3]. By targeting unique bacterial enzymes such as cobalamin synthase (CobS) or cobaltochelatases, researchers aim to develop therapies that exhibit high selective toxicity without interfering with human metabolism [4]. Current therapeutic interest focuses on disrupting this pathway to overcome antibiotic resistance in chronic bacterial infections [5]. (Citations: [1] PubMed ID: 29433108, [2] UniProt Biological Process: GO:0009236, [3] PubMed ID: 25411286, [4] PubMed ID: 17606360, [5] NIH/PMC: PMC4121659)

Other names

Vitamin B12 biosynthetic pathwayCorrinoid biosynthesis pathwayDe novo cobalamin synthesisAnaerobic/aerobic cobalamin pathway

Inhibition of specific biosynthetic enzymes within the pathway (e.g., CobS, CobU, or CbiA) to prevent the production of essential cobalamin cofactors in pathogens, leading to metabolic arrest.