Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 114, Issue 7, Pages E1205-E1214Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1612360114
Keywords
chemical biology; cobalamin; metabolism; microbial regulation
Categories
Funding
- US Department of Energy (DOE), Office of Biological and Environmental Research (OBER), BER's Genomic Science Program
- US DOE [DE-AC05-76RL01830]
- Russian Foundation for Basic Research [14-04-00870]
- Russian Academy of Sciences via the program Molecular and Cellular Biology
- OBER
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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.
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