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Aerobic methane-oxidizing bacteria or methanotrophs have the unique ability to grow on methane as their sole source of carbon and energy. The main metabolic steps of the methane utilization by microorganisms have been identified and well-studied to date. However, a detailed understanding of molecular genetic mechanisms that provide an adaptive response at the level of transcription regulation to various growth conditions, high and low pH, temperature, and salinity is still elusive. To solve the issue we have conducted a detailed theoretical study of the molecular mechanisms of gene expression regulation in the bacterium Methylotuvimicrobium alcaliphilum 20ZR (hereinafter 20ZR) based on the integration of original omics data into genome-scale metabolic model of the 20ZR.