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

Abstract

Only a small fraction of vitamin B₁₂-requiring organisms are able to synthesize B₁₂ 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 B₁₂-binding enzymes and regulatory roles for B₁₂ Here we report the development and use of a B₁₂-based chemical probe to identify B₁₂-binding proteins in a nonphototrophic B₁₂-producing bacterium. Two unexpected discoveries resulted from this study. First, we identified a light-sensing B₁₂-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. These metabolic processes produce precursors for synthesis of DNA, RNA, and protein. Thereby, B₁₂ likely modulates growth, and by limiting its availability to auxotrophs, B₁₂-producing organisms may facilitate coordination of community metabolism.