Methanotrophs: Metabolic versatility from utilization of methane to multi-carbon sources and perspectives on current and future applications.

[Display omitted] • pMMO-related features provide the groundwork for methane-based biomanufacturing. • Multi-carbon utilization reprograms the substrate spectrum of methanotrophs. • Harnessing methanotrophs as robust microbial chassis is now being developed. • Inherent advantages can be exploited to enhance the production of various products. The development of biorefineries for a sustainable bioeconomy has been driven by the concept of utilizing environmentally friendly and cost-effective renewable energy sources. Methanotrophic bacteria with a unique capacity to utilize methane as a carbon and energy source can serve as outstanding biocatalysts to develop C1 bioconversion technology. By establishing the utilization of diverse multi-carbon sources, integrated biorefinery platforms can be created for the concept of the circular bioeconomy. An understanding of physiology and metabolism could help to overcome challenges for biomanufacturing. This review summaries fundamental gaps for methane oxidation and the capability to utilize multi-carbon sources in methanotrophic bacteria. Subsequently, breakthroughs in harnessing methanotrophs as robust microbial chassis for industrial biotechnology were compiled and overviewed. Finally, challenges and capabilities to exploit the inherent advantages of methanotrophs to synthesize various target products in higher titers are proposed. [ABSTRACT FROM AUTHOR]