| Cobamides are essential cofactors that are widely distributed in nature. These large, complex molecules are found in all domains of life and are involved in processes central to cell physiology, including nucleic acid synthesis, fatty acid metabolism, and energy generation. Although all eukaryotes, with the exception of higher plants, are known to require cobamides, their de novo synthesis appears to be limited to bacteria and archaea. Extensive research has been conducted into cobamide biosynthesis and utilization in bacteria such as Pseudomonas denitrificans and Salmonella enterica, but much less is known about the synthesis and roles of cobamides in archaea. The work described in this dissertation focuses primarily on the identification and characterization of enzymes involved in the final steps of cobamide biosynthesis -- in particular, the synthesis of the cobamide adenosylcobalamin (a.k.a. coenzyme B12) -- in the bacterium S. enterica and in the hyperthermophilic archaeon Methanocaldococcus jannaschii. |
