Engineered methane biocatalysis: strategies to assimilate methane for chemical production

Methane (CH₄), one of the greenhouse gases, is considered a promising feedstock for the biological production of fuels and chemicals. Although recent studies have demonstrated the capability of methanotrophs to convert CH₄ into various bioproducts by metabolic engineering, the productivity has not reached commercial levels. As such, there is a growing interest in synthetic methanotrophic systems as an alternative. This review summarizes the strategies for enhancing native CH₄ assimilation and discusses the challenges for the construction of synthetic methanotrophy into nonmethanotrophic industrial strains. Additionally, we suggest a mixed heterotrophic approach that integrates CH₄ assimilation with glucose and xylose metabolism to improve productivity. The synthetic methanotrophic system presented in this review could pave the way for sustainable and efficient biomanufacturing using CH₄.