Vitamin B12 (cyanocobalamin) is the normal isolated form of coenzyme B12 (adenosylcobalamin), a structure of marvellous architecture and amazing biological activity. It belongs to the family of tetrapyrroles which includes inter alia the haems and the chlorophylls. This review begins with a brief overview of the biosynthesis of tetrapyrroles in general but then concentrates on recent research on B12 biosynthesis. The first main section reviews the biosynthesis of uro'gen III, the last common precursor of all natural tetrapyrroles, concentrating particularly on the three enzymes, porphobilinogen synthase, hydroxymethylbilane synthase and uro'gen III synthase. Crystal structures are available for the second of these enzymes and a new proposal is presented for its detailed mode of action. The second main section reviews the recent discovery of the complete biosynthetic pathway from uro'gen III to hydrogen- obyrinic acid in Pseudomonas denitrificans, which has revealed some beautiful and totally unexpected chemistry. A short section then describes the many similarities and some differences in the chemistry used by the micro-aerophilic organism Propionibacterium shermanii for the synthesis of coenzyme B12 compared with that seen in the aerobic Ps. denitrificans. Finally an account is given of the remarkable steps needed to complete the synthesis of the coenzyme in both organisms.
Department of Chemistry
University of Cambridge