Genome-scale metabolic models (GEMs) are valuable tools serving systems biology and metabolic engineering. However, GEMs are still an underestimated tool in informing microbial ecology. Since their first application for aerobic gammaproteobacterial methane oxidizers less than a decade ago, GEMs have substantially increased our understanding of the metabolism of methanotrophs, a microbial guild of high relevance for the natural and biotechnological mitigation of methane efflux to the atmosphere. Particularly, GEMs helped to elucidate critical metabolic and regulatory pathways of several methanotrophic strains, predicted microbial responses to environmental perturbations, and were used to model metabolic interactions in cocultures. Here, we conducted a systematic review of GEMs exploring aerobic methanotrophy, summarizing recent advances, pointing out weaknesses, and drawing out probable future uses of GEMs to improve our understanding of the ecology of methane oxidizers. We also focus on their potential to unravel causes and consequences when studying interactions of methane-oxidizing bacteria with other methanotrophs or members of microbial communities in general. This review aims to bridge the gap between applied sciences and microbial ecology research on methane oxidizers as model organisms and to provide an outlook for future studies.

Department of Biological Sciences Faculty of Science University of Alberta Edmonton AB T6G 2E9 Canada

Department of Chemical Engineering and Environmental Technology School of Industrial Engineering University of Valladolid Valladolid 47011 Spain

Department of Ecosystem Biology Faculty of Science University of South Bohemia 370 05 České Budějovice Czech Republic

Department of Science Laboratory Technology Faculty of Physical Sciences University of Nigeria Nsukka 410001 Nigeria

Institute of Soil Biology and Biogeochemistry Biology Centre CAS 370 05 České Budějovice Czech Republic

Institute of Sustainable Processes Valladolid 47011 Spain

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