Vitamin B12: Insights into Biosynthesisʹs Mount Improbable

The biosynthesis of the corrin ring component of cobalamin (vitamin B12) is reviewed with regard to how two separate though broadly similar pathways may have evolved. The more ancient “anaerobic” pathway is characterized by the early chelation of cobalt and the release of acetaldehyde whereas the “aerobic” pathway is characterized by an absolute dependency on molecular oxygen, the late chelation of cobalt and the release of acetic acid. Both pathways require the addition of 8S-adenosyl-L-methionine-derived methyl groups to the periphery of the tetrapyrrole framework. The sequences of these enzymes reveal that they are clearly related, most likely having evolved from an ancestral methylase gene. The three-dimensional structure of one of these methyltransferases is highlighted and discussed in light of a common mechanism for this family of enzymes. Moreover, the aerobic and anaerobic chelatases are described and parallels with the chelatases found in heme and chlorophyll synthesis are drawn.