Biosynthesis and Use of Cobalamin (B12).

This review summarizes research performed over the last 23 years on the genetics, enzyme structures and functions, and regulation of the expression of the genes encoding functions involved in adenosylcobalamin (AdoCbl, or coenzyme B12) biosynthesis. It also discusses the role of coenzyme B12 in the physiology of Salmonella enterica serovar Typhimurium LT2 and Escherichia coli. John Roth's seminal contributions to the field of coenzyme B12 biosynthesis research brought the power of classical and molecular genetic, biochemical, and structural approaches to bear on the extremely challenging problem of dissecting the steps of what has turned out to be one of the most complex biosynthetic pathways known. In E. coli and serovar Typhimurium, uro'gen III represents the first branch point in the pathway, where the routes for cobalamin and siroheme synthesis diverge from that for heme synthesis. The cobalamin biosynthetic pathway in P. denitrificans was the first to be elucidated, but it was soon realized that there are at least two routes for cobalamin biosynthesis, representing aerobic and anaerobic variations. The expression of the AdoCbl biosynthetic operon is complex and is modulated at different levels. At the transcriptional level, a sensor response regulator protein activates the transcription of the operon in response to 1,2-Pdl in the environment. Serovar Typhimurium and E. coli use ethanolamine as a source of carbon, nitrogen, and energy. In addition, and unlike E. coli, serovar Typhimurium can also grow on 1,2-Pdl as the sole source of carbon and energy.