Paper
Elucidation of roles for vitamin B12 in regulation of folate, ubiquinone, and methionine metabolism
Published Jan 30, 2017 · M. Romine, D. Rodionov, Y. Maezato
Proceedings of the National Academy of Sciences
78
Citations
2
Influential Citations
Abstract
Significance Using a chemical probe mimic of vitamin B12, we reveal a light- and B12-dependent DNA regulator, and make the unexpected discovery of B12 having regulatory involvement in microbial folate, ubiquinone, and methionine processes. These findings suggest a pivotal role for B12 in the control of cell growth, which may lead to coordination of cell behavior in complex multicellular systems. As key research questions emerge from host-associated and environmental microbiomes, we anticipate that B12 regulatory control of metabolism will be found to be generalizable, will be critical for coordination of individual microbe and community metabolism, and that organismal interdependencies for B12 may be pertinent to microbiome organization, stability, and overall function. 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.
Vitamin B12 plays a crucial role in regulating microbial folate, ubiquinone, and methionine metabolism, potentially affecting cell growth and community metabolism coordination.
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