COBALAMIN (COENZYME B-12) - SYNTHESIS AND BIOLOGICAL SIGNIFICANCE

This review examines deoxyadenosylcobalamin (Ado-B-12) biosynthesis, t ransport, use, and uneven distribution among living forms. We describe how genetic analysis of enteric bacteria has contributed to these iss ues. Two pathways for corrin ring formation have been found-an aerobic pathway (in P. denitrificans) and an anaerobic pathway (in P. sherman ii and S. typhimurium)-that differ in the point of cobalt insertion. A nalysis of B-12 transport in E. coli reveals two systems: one (with tw o proteins) for the outer membrane, and one (with three proteins) for the inner membrane. To account for the uneven distribution of B-12 in living forms, we suggest that the B-12 synthetic pathway may have evol ved to allow anaerobic fermentation of small molecules in the absence of an external electron acceptor. Later, evolution of the pathway prod uced siroheme, (allowing use of inorganic electron accepters), chlorop hyll (O-2 production), and heme (aerobic respiration). As oxygen becam e a larger part of the atmosphere, many organisms lost fermentative fu nctions and retained dependence on newer, B-12 functions that did not involve fermentation. Paradoxically, Salmonella spp. synthesize B-12 o nly anaerobically but can use B-12 (for degradation of ethanolamine an d propanediol) only with oxygen. Genetic analysis of the operons for t hese degradative functions indicate that anaerobic degradation is impo rtant. Recent results suggest that Bit can be synthesized and used dur ing anaerobic respiration using tetrathionate (but not nitrate or fuma rate) as an electron acceptor. The branch of enteric taxa from which S almonella spp, and E. coli evolved appears to have lost the ability to synthesize B-12 and the ability to use it in propanediol and glycerol degradation. Salmonella spp., but not E. coli, have acquired by horiz ontal transfer the ability to synthesize B-12 and degrade propanediol. The acquired ability to degrade propanediol provides the selective fo rce that maintains B-12 synthesis in this group.