title: Methanobactin and MmoD work in concert to act as the 'copper-switch' in methanotrophs.
abstract: Biological oxidation of methane to methanol by aerobic bacteria is catalysed by two different enzymes, the cytoplasmic or soluble methane monooxygenase (sMMO) and the membrane-bound or particulate methane monooxygenase (pMMO). Expression of MMOs is controlled by a 'copper-switch', i.e. sMMO is only expressed at very low copper : biomass ratios, while pMMO expression increases as this ratio increases. Methanotrophs synthesize a chalkophore, methanobactin, for the binding and import of copper. Previous work suggested that methanobactin was formed from a polypeptide precursor. Here we report that deletion of the gene suspected to encode for this precursor, mbnA, in Methylosinus trichosporium OB3b, abolishes methanobactin production. Further, gene expression assays indicate that methanobactin, together with another polypeptide of previously unknown function, MmoD, play key roles in regulating expression of MMOs. Based on these data, we propose a general model explaining how expression of the MMO operons is regulated by copper, methanobactin and MmoD. The basis of the 'copper-switch' is MmoD, and methanobactin amplifies the magnitude of the switch. Bioinformatic analysis of bacterial genomes indicates that the production of methanobactin-like compounds is not confined to methanotrophs, suggesting that its use as a metal-binding agent and/or role in gene regulation may be widespread in nature.
authors.affiliation: Department of Civil and Environmental Engineering, University of Michigan, Ann Arbor, MI 48109-2125, USA.
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Semrau
authors.affiliation: Department of Civil and Environmental Engineering, University of Michigan, Ann Arbor, MI, 48109-2125, USA.
authors.forename: Sheeja
authors.initials: S
authors.lastname: Jagadevan
authors.affiliation: Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA, 50011, USA.
authors.forename: Alan A
authors.initials: AA
authors.lastname: DiSpirito
authors.affiliation: School of Life Sciences, University of Warwick, Coventry, CV4 7AL, UK.|Botany Department, Faculty of Science, Beni-Suef University, Beni-Suef, 65211, Egypt.
authors.forename: Ashraf
authors.initials: A
authors.lastname: Khalifa
authors.affiliation: School of Life Sciences, University of Warwick, Coventry, CV4 7AL, UK.
authors.forename: Julie
authors.initials: J
authors.lastname: Scanlan
authors.affiliation: Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA, 50011, USA.
authors.forename: Brandt H
authors.initials: BH
authors.lastname: Bergman
authors.affiliation: Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA, 50011, USA.
authors.forename: Brittani C
authors.initials: BC
authors.lastname: Freemeier
authors.affiliation: Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA, 50011, USA.
authors.forename: Bipin S
authors.initials: BS
authors.lastname: Baral
authors.affiliation: Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA, 50011, USA.
authors.forename: Nathan L
authors.initials: NL
authors.lastname: Bandow
authors.affiliation: Department of Civil and Environmental Engineering, University of Michigan, Ann Arbor, MI, 48109-2125, USA.
authors.forename: Alexey
authors.initials: A
authors.lastname: Vorobev
authors.affiliation: J. Craig Venter Institute, 9704 Medical Center Drive, Rockville, MD, 20850, USA.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Haft
authors.affiliation: Equipe Adaptations et Interactions Microbiennes dans l'Environnement, Département Micro-organismes, Génomes, Environnement, UMR 7156 Université de Strasbourg - CNRS, Université de Strasbourg, 67083, Strasbourg Cédex, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Vuilleumier
authors.affiliation: School of Environmental Sciences, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK.
authors.forename: J Colin
authors.initials: JC
authors.lastname: Murrell
mesh_terms: D001692:Biological Transport; D003300:Copper / Q000378:metabolism*; D017353:Gene Deletion; D015870:Gene Expression; D015964:Gene Expression Regulation, Bacterial; D007093:Imidazoles / Q000378:metabolism*; D008697:Methane / Q000378:metabolism; D000432:Methanol / Q000378:metabolism; D020602:Methylosinus trichosporium / Q000235:genetics* / Q000378:metabolism; D009842:Oligopeptides / Q000096:biosynthesis / Q000378:metabolism*; D009876:Operon; D010084:Oxidation-Reduction; D010105:Oxygenases / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*
chemical_list: D007093:Imidazoles; D009842:Oligopeptides; C491147:methanobactin; D003300:Copper; D010105:Oxygenases; C021555:methane monooxygenase; D008697:Methane; D000432:Methanol