title: Elucidation of roles for vitamin B12in regulation of folate, ubiquinone, and methionine metabolism.
abstract: Only a small fraction of vitamin B12-requiring organisms are able to synthesize B12de 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 B12Here 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, B12likely modulates growth, and by limiting its availability to auxotrophs, B12-producing organisms may facilitate coordination of community metabolism.
authors.affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352.
authors.forename: Margaret F
authors.initials: MF
authors.lastname: Romine
authors.affiliation: 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.
authors.forename: Dmitry A
authors.initials: DA
authors.lastname: Rodionov
authors.affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Maezato
authors.affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352.
authors.forename: Lindsey N
authors.initials: LN
authors.lastname: Anderson
authors.affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352.
authors.forename: Premchendar
authors.initials: P
authors.lastname: Nandhikonda
authors.affiliation: Department of Bioinformatics, Sanford-Burnham-Prebys Medical Discovery Institute, La Jolla, CA 92037.
authors.forename: Irina A
authors.initials: IA
authors.lastname: Rodionova
authors.affiliation: Department of Bioengineering, Polytech Nice-Sophia, 06410 Biot, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Carre
authors.affiliation: Department of Bioinformatics, Sanford-Burnham-Prebys Medical Discovery Institute, La Jolla, CA 92037.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Li
authors.affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352.
authors.forename: Chengdong
authors.initials: C
authors.lastname: Xu
authors.affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352.
authors.forename: Therese R W
authors.initials: TR
authors.lastname: Clauss
authors.affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352.
authors.forename: Young-Mo
authors.identifier: 0000-0002-8972-7593
authors.initials: YM
authors.lastname: Kim
authors.affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352.
authors.forename: Thomas O
authors.initials: TO
authors.lastname: Metz
authors.affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352; aaron.wright@pnnl.gov.
authors.forename: Aaron T
authors.initials: AT
authors.lastname: Wright
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D001669:Biochemical Phenomena / Q000528:radiation effects; D005492:Folic Acid / Q000378:metabolism*; D020563:Gammaproteobacteria / Q000235:genetics / Q000378:metabolism; D020632:Halomonas / Q000235:genetics / Q000378:metabolism*; D008715:Methionine / Q000378:metabolism*; D011485:Protein Binding / Q000528:radiation effects; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D014451:Ubiquinone / Q000378:metabolism*; D014466:Ultraviolet Rays; D014805:Vitamin B 12 / Q000737:chemistry / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D014451:Ubiquinone; D005492:Folic Acid; D008715:Methionine; D014805:Vitamin B 12
keywords: chemical biology; cobalamin; metabolism; microbial regulation