VitaminB12and CofactorF430

Vitamin B 12 and other cobalt-corrins, as well the nickel-hydrocorphinoid cofactor F430, are extraordinary natural porphyrinoids that enrich the biochemical arsenal of the “pigments of life.” The red cobalt-corrin vitamin B 12 was discovered as the result of the search for the cause of “pernicious anemia.” The yellow Ni-hydrocorphin F430 was identified as a cofactor in methane formation by methanogenic archaea. Cobalt-corrins have acquired a broad spectrum of biological roles in the course of evolution. B 12 -derivatives are particularly important as catalysts in the basic metabolism of microorganisms. Cobalamins play a remarkably specific metabolic role in humans and other mammals, where methylcobalamin ( MeCbl ) and coenzyme B 12 are two B 12 -cofactors indispensable for catalysis of methyl group transfer by methionine synthase, and of a radical rearrangement by methylmalonyl-CoA mutase ( MCM ), respectively. Recent insights from biology and biomedicine, as well as synthetic advances supported by modern biotechnology are presented, which have made research on cobalamins ( Cbl's ) and related corrinoids a thriving field holding promise of further exciting discoveries. The only known biological role of the Ni-hydrocorphin F430 is as the prosthetic group of methyl-coenzyme reductase ( MCR ), the enzyme catalyzing the key step of methane formation and the anaerobic oxidation of methane ( AOM ) by archaea. The active enzyme contains the central metal in the rare Ni I oxidation state. We discuss how Nature has tuned the structure of the tetrapyrrolic ligand to make reduction to Ni I possible. The catalytic mechanism is still under investigation, but recent results point to a radical mechanism. The focus of this chapter is recent discoveries concerning the structure, biological formation, chemical reactivity, biomolecular binding, mode of action, and metabolic relevance as cofactors of cobalt-corrins and nickel-hydrocorphins.