CHAPTER 1 INTRODUCTION In 1926, Minot and Murphy discovered that a diet containing high amounts of liver would prevent death in individuals suffering from pernicious anemia (Minot and Murphy 1926). It was not until 1948 that two independent research teams led by K. Folkers and E.L. Smith isolated the active component of this liver diet and agreed to name it vitamin B12 (Rickes et al. 1948, Smith and Parker 1948). In 1950, these research teams joined two additional teams (led by Sir Alexander Todd and D. C. Hodgkin), and solved the chemical structure of B12 in the ensuing 6 years (Hodgkin et al. 1955). Soon after, Lenhert and Hodgkin solved the structure of a newly discovered coenzymatic form of B12, adenosyl-B12 (Ado-B12) (Lenhert and Hodgkin 1961). In the next year yet another coenzymatic form of B12 was discovered (methyl-B12), which was found to be a cofactor for methionine synthase (Guest et al. 1962a, Guest et al. 1962b). By 1972, more than ten coenzyme B12-dependent enzymes or enzyme systems had been discovered and characterized (Schneider 1987). Presently, at least fifteen coenzyme B12-dependent enzymes are known (Schneider 1987, Roth et al. 1996). Vitamin B12 is required for methionine synthesis and propionate catabolism in higher animals. Among prokaryotes, it appears to play an important role in a number of metabolic pathways that have ecological and industrial significance including several amino acid and carbohydrate fermentations, methane production, carbon dioxide fixation via the acetyl-CoA pathway (Wood et al. 1986, Ragsdale 1991, Stupperich 1993, Ferry 1995), acetogenesis (Lj ungdahl 1982, Ragsdale 1991), ribonucleotide reduction, (Blakley