Mechanistic and evolutionary aspects of vitamin B12 biosynthesis
For the past 20 years our laboratory has been engaged in the elucidation of the vitamin B12 biosynthetic pathway and a previous Account1 described progress made in the first ten years of this endeavor. By that time (1977), it had been established that 5-aminolevulinic acid (ALA), porphobilinogen (PBG) uro’gen III and three intermediates, Factors I–III, now known to be transformed as the precorrins 1–3, were sequentially formed on the way to the corrin nucleus as summarized in Scheme 1. The ensuing decade has witnessed an exponential increase in the rate of the acquisition of pure enzymes using recombinant DNA techniques and these methods together with the exploration of new NMR pulse sequences have not only cast light on the mechanisms of the B12 synthetic enzymes but have given us considerable optimism with regard to the discovery of the remaining intermediates and of the enzymes which produce them.