Cobalamin biosynthesis is the process by which bacteria and archea make cobalamin, vitamin B12. Many steps are involved in converting aminolevulinic acid via uroporphyrinogen III and adenosylcobyric acid to the final forms in which it is used by enzymes in both the producing organisms and other species, including humans who acquire it through their diet.
The feature which distinguishes the two main biosynthetic routes is whether the cobalt that is at the catalytic site in the coenzyme is incorporated early (in anaerobic organisms) or late (in aerobic organisms) and whether oxygen is required. In both cases, the macrocycle that will form a coordination complex with the cobalt ion is a corrin ring, specifically one with seven carboxylate groups called cobyrinic acid. Subsequently, amide groups are formed on all but one of the carboxylates, giving cobyric acid, and the cobalt is ligated by an adenosyl group. In the final part of the biosynthesis, common to all organisms, an aminopropanol sidechain is added to the one free carboxylic group and assembly of the nucleotide loop, which will provide the second ligand for the cobalt, is completed.
Many prokaryotic species cannot biosynthesize adenosylcobalamin, but can make it from cobalamin which they assimilate from external sources. In humans, dietary sources of cobalamin are bound after ingestion as transcobalamins and converted to the coenzyme forms in which they are used.