Cobalamin (coenzyme B12): synthesis and biological significance.

This review examines deoxyadenosylcobalamin (Ado-B12) biosynthesis, transport, use, and uneven distribution among living forms. We describe how genetic analysis of enteric bacteria has contributed to these issues. Two pathways for corrin ring formation have been found-an aerobic pathway (in P. denitrificans) and an anaerobic pathway (in P. shermanii and S. typhimurium)-that differ in the point of cobalt insertion. Analysis of B12 transport in E. coli reveals two systems: one (with two proteins) for the outer membrane, and one (with three proteins) for the inner membrane. To account for the uneven distribution of B12 in living forms, we suggest that the B12 synthetic pathway may have evolved to allow anaerobic fermentation of small molecules in the absence of an external electron acceptor. Later, evolution of the pathway produced siroheme, (allowing use of inorganic electron acceptors), chlorophyll (O2 production), and heme (aerobic respiration). As oxygen became a larger part of the atmosphere, many organisms lost fermentative functions and retained dependence on newer, B12 functions that did not involve fermentation. Paradoxically, Salmonella spp. synthesize B12 only anaerobically but can use B12 (for degradation of ethanolamine and propanediol) only with oxygen. Genetic analysis of the operons for these degradative functions indicate that anaerobic degradation is important. Recent results suggest that B12 can be synthesized and used during anaerobic respiration using tetrathionate (but not nitrate or fumarate) as an electron acceptor. The branch of enteric taxa from which Salmonella spp. and E. coli evolved appears to have lost the ability to synthesize B12 and the ability to use it in propanediol and glycerol degradation. Salmonella spp., but not E. coli, have acquired by horizontal transfer the ability to synthesize B12 and degrade propanediol. The acquired ability to degrade propanediol provides the selective force that maintains B12 synthesis in this group.