skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Elucidation of roles for vitamin B 12 in regulation of folate, ubiquinone, and methionine metabolism

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America
 [1];  [2];  [1];  [1];  [1];  [3];  [4];  [3];  [1];  [1]; ORCiD logo [1];  [1];  [1]
  1. Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352,
  2. Department of Microbial Genomics, A. A. Kharkevich Institute for Information Transmission Problems, Russian Academy of Sciences, Moscow 127994, Russia,, Department of Bioinformatics, Sanford-Burnham-Prebys Medical Discovery Institute, La Jolla, CA 92037,
  3. Department of Bioinformatics, Sanford-Burnham-Prebys Medical Discovery Institute, La Jolla, CA 92037,
  4. Department of Bioengineering, Polytech Nice-Sophia, 06410 Biot, France

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 new 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. Furthermore, B12 modulates growth, and by limiting its availability to auxotrophs, B12-producing organisms may facilitate coordination of community metabolism.

Research Organization:
Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
Sponsoring Organization:
USDOE
Grant/Contract Number:
58612; AC05-76RL01830
OSTI ID:
1341767
Alternate ID(s):
OSTI ID: 1347852
Report Number(s):
PNNL-SA-119181
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Vol. 114 Journal Issue: 7; ISSN 0027-8424
Publisher:
Proceedings of the National Academy of SciencesCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 55 works
Citation information provided by
Web of Science

References (41)

Traveling the Vitamin B 12 Pathway: Oral Delivery of Protein and Peptide Drugs journal January 2009
Design, Synthesis, and Characterization of Fluorescent Cobalamin Analogues with High Quantum Efficiencies journal June 2009
Synthesis of LHRH Antagonists Suitable for Oral Administration via the Vitamin B 12 Uptake System. journal January 1995
DAnTE: a statistical tool for quantitative analysis of -omics data journal May 2008
Structural basis for gene regulation by a B12-dependent photoreceptor journal September 2015
Comparative Genomics of the Vitamin B 12 Metabolism and Regulation in Prokaryotes journal July 2003
Vitamin B12 transport from food to the body's cells—a sophisticated, multistep pathway journal May 2012
The biosynthesis of adenosylcobalamin (vitamin B12) journal June 2002
Ultrasensitive Proteomics Using High-Efficiency On-Line Micro-SPE-NanoLC-NanoESI MS and MS/MS journal January 2004
Singlet Halophenylcarbenes as Strong Hydrogen-Bond Acceptors journal May 2016
Rearrangement of Dimethylcarbene to Propene:  Study by Laser Flash Photolysis and ab Initio Molecular Orbital Theory journal May 1998
Biochemical and Spectroscopic Studies of Epoxyqueuosine Reductase: A Novel Iron–Sulfur Cluster- and Cobalamin-Containing Protein Involved in the Biosynthesis of Queuosine journal July 2015
A subset of the diverse COG0523 family of putative metal chaperones is linked to zinc homeostasis in all kingdoms of life journal January 2009
Synthesis and Characterization of Fluorescent Cobalamin (CobalaFluor) Derivatives for Imaging journal March 2001
Involvement of CarA/LitR and CRP/FNR Family Transcriptional Regulators in Light-Induced Carotenoid Production in Thermus thermophilus journal March 2011
Synthesis and Characterization of a Cobalamin−Colchicine Conjugate as a Novel Tumor-Targeted Cytotoxin journal December 2004
Structural Determination of 5‘-OH α-Ribofuranoside Modified Cobalamins via 13 C and DEPT NMR journal September 2003
Multiplexed Activity-based Protein Profiling of the Human Pathogen Aspergillus fumigatus Reveals Large Functional Changes upon Exposure to Human Serum journal August 2012
Human Gut Microbes Use Multiple Transporters to Distinguish Vitamin B12 Analogs and Compete in the Gut journal January 2014
Identification of Widespread Adenosine Nucleotide Binding in Mycobacterium tuberculosis journal January 2013
Development of a Simplified Method for the Determination of Folates in Baker's Yeast by HPLC with Ultraviolet and Fluorescence Detection journal April 2005
Abundance and functional diversity of riboswitches in microbial communities journal January 2007
Regulation of the vitamin B12 metabolism and transport in bacteria by a conserved RNA structural element journal September 2003
Synthesis of Cobalamin−Biotin Conjugates That Vary in the Position of Cobalamin Coupling. Evaluation of Cobalamin Derivative Binding to Transcobalamin II journal January 1996
“Clickable” Vitamin B 12 Derivative journal January 2013
A diazirine-based photoaffinity etoposide probe for labeling topoisomerase II journal January 2010
RegPredict: an integrated system for regulon inference in prokaryotes by comparative genomics approach journal June 2010
Equilibrium and Kinetic Analyses of the Interactions between Vitamin B12 Binding Proteins and Cobalamins by Surface Plasmon Resonance journal June 2002
The photochemical mechanism of a B12-dependent photoreceptor protein journal August 2015
Spectral Probabilities and Generating Functions of Tandem Mass Spectra: A Strike against Decoy Databases journal August 2008
COBALAMIN (COENZYME B 12 ): Synthesis and Biological Significance journal October 1996
Live Cell Discovery of Microbial Vitamin Transport and Enzyme-Cofactor Interactions journal December 2015
Knock-out of SO1377 gene, which encodes the member of a conserved hypothetical bacterial protein family COG2268, results in alteration of iron metabolism, increased spontaneous mutation and hydrogen peroxide sensitivity in Shewanella oneidensis MR-1 journal April 2006
Vitamin B 12 as a Modulator of Gut Microbial Ecology journal November 2014
Beyond catalysis: vitamin B 12 as a cofactor in gene regulation : B12 in gene regulation journal January 2014
Role and Function of LitR, an Adenosyl B 12 -Bound Light-Sensitive Regulator of Bacillus megaterium QM B1551, in Regulation of Carotenoid Production journal April 2015
Light-dependent gene regulation by a coenzyme B12-based photoreceptor journal April 2011
Live Cell Chemical Profiling of Temporal Redox Dynamics in a Photoautotrophic Cyanobacterium journal October 2013
Comparative Genomic Reconstruction of Transcriptional Regulatory Networks in Bacteria journal July 2007
RegPrecise 3.0 – A resource for genome-scale exploration of transcriptional regulation in bacteria journal January 2013
Versatile PCR-mediated insertion or deletion mutagenesis journal March 2004