Elucidation of roles for vitamin B12 in regulation of folate, ubiquinone, and methionine metabolism

Only a small fraction of vitamin B-12-requiring organisms are able to synthesize B-12 de novo, making it a common commodity in microbial communities. Initially recognized as an enzyme cofactor of a few enzymes, recent studies have revealed additional B-12-binding enzymes and regulatory roles for B-12. Here we report the development and use of a B-12-based chemical probe to identify B-12-binding proteins in a nonphototrophic B-12-producing bacterium. Two unexpected discoveries resulted from this study. First, we identified a light-sensing B-12-binding transcriptional regulator and demonstrated that it controls folate and ubiquinone biosynthesis. Second, our probe captured proteins involved in folate, methionine, and ubiquinone metabolism, suggesting that it may play a role as an allosteric effector of these processes. Thesemetabolic processes produce precursors for synthesis of DNA, RNA, and protein. Thereby, B-12 likely modulates growth, and by limiting its availability to auxotrophs, B-12-producing organisms may facilitate coordination of community metabolism.