Genome Scale Metabolic Models (GSMMs) of the recently sequenced Methylocystis hirsuta and two other methanotrophs from the genus Methylocystis have been reconstructed. These organisms are Type II methanotrophs with the ability of accumulating Polyhydroxyalkanoates under nutrient limiting conditions. For the first time, GSMMs have been reconstructed for Type II methanotrophs. These models, combined with experimental biomass and PHB yields of Methylocystis hirsuta, allowed elucidating the methane oxidation mechanism by the enzyme pMMO (particulate methane monooxygenase) in these organisms. In contrast to Type I methanotrophs, which use the "direct coupling mechanism", Type II methanotrophs appear to use the so called "redox arm mechanism". The utilization of the "redox arm mechanism", which involves the coupling between methane oxidation and complex I of the respiratory chain, was confirmed by inhibition of complex I with catechol. Utilization of the "redox arm" mechanism leads to lower biomass yields on methane compared to Type I methanotrophs. However, the ability of Type II metanotrophs to redirect high metabolic carbon fluxes towards acetoacetyl-CoA under nitrogen limiting conditions makes these organisms promising platforms for metabolic engineering.

Methane, with a global warming potential twenty five times higher than that of CO is the second most important greenhouse gas emitted nowadays. Its bioconversion into microbial molecules with a high retail value in the industry offers a potential cost-efficient and environmentally friendly solution for mitigating anthropogenic diluted CH-laden streams. Methane bio-refinery for the production of different compounds such as ectoine, feed proteins, biofuels, bioplastics and polysaccharides, apart from new bioproducts characteristic of methanotrophic bacteria, has been recently tested in discontinuous and continuous bioreactors with promising results. This review constitutes a critical discussion about the state-of-the-art of the potential and research niches of biotechnologies applied in a CH biorefinery approach.

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