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Environ Microbiol. 2013 Nov;15(11):3077-86. doi: 10.1111/1462-2920.12150. Epub 2013 May 20.

Methanobactin and MmoD work in concert to act as the 'copper-switch' in methanotrophs.

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Department of Civil and Environmental Engineering, University of Michigan, Ann Arbor, MI 48109-2125, USA.
Department of Civil and Environmental Engineering, University of Michigan, Ann Arbor, MI, 48109-2125, USA.
Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA, 50011, USA.
School of Life Sciences, University of Warwick, Coventry, CV4 7AL, UK.
Botany Department, Faculty of Science, Beni-Suef University, Beni-Suef, 65211, Egypt.
J. Craig Venter Institute, 9704 Medical Center Drive, Rockville, MD, 20850, USA.
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.
School of Environmental Sciences, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK.


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.

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