Conversion of Cobinamide into Coenzyme B12

Cobamides are unique cyclic tetrapyrroles because their structures include an upper (Coβ) and a lower (Coα) axial ligand. The Coα and Coβ ligands are important for the interaction of the cobamide with enzymes, and for the chemistry of the reaction catalyzed by the enzyme. B12 (5,6-dimethylbenzimidazolylcobamide, cobalamin) is the best-known cobamide, which in its vitamin form has a cyano group as Coβ ligand, and in its coenzymic form it has a 5′-deoxyadenosine group as Coβ ligand (Fig. 1). In this chapter we review the current understanding of upper and lower ligand attachment to the ring macrocycle. Most of the knowledge reviewed here was obtained using bacterial systems; we add to the discussion recent work from our laboratory that uncovered variations in the conversion of cobinamide to B12 in archaea.