Vitamin B_(12): How the Problem of Its Biosynthesis Was Solved

摘要

Vitamin B,, is an essential vitamin for human health, and lack of it leads to pernicious anemia. This biological activity has attracted intense interest for some time; in addition, the complex architecture of the B_(12) molecule has fascinated chemists and biochemists since its discovery as the first natural organo-cohalt complex and the establishment of its structure by X-ray analysis. The organic ligand surrounding the cobalt displays many stereogenic centers along its periphery carrying reactive functional groups. This complexity led vitamin B_(12) to be rightly regarded as an extreme challenge to the synthetic chemist. Yet microorganisms achieve this synthesis in vivo with complete control of regio- and stereochemistry. How do they do it? This review tells the full remarkable story. Success in unraveling this biosyn-thetic puzzle resulted from a collaborative effort by biologists and chemists using the full range of methods available from their disciplines— from genetics at one end of the spectrum to synthesis and NMR spectroscopv at the other. This work can act as a guide for future research on the biosynthesis of yet more complex natural substances.