Outlook on engineering methylotrophs for one-carbon-based industrial biotechnology

Methane and carbon dioxide (CO2) account for the most abundant greenhouse gases (GHGs). The removal of atmospheric methane and CO2 is an urgent mission contributing to the minimization of climate change. In this context, the methylotrophic bacteria-based technologies capturing and assimilating methane, CO2 and methane/ CO2 derivatives, such as methanol and formate, are promising to reduce atmospheric methane and CO2. Herein, we emphasized the outstanding of methylotrophs in bioconversion of methane, CO2, methanol and formate, which are regarded as one-carbon (C1) substrates. Innovative strategies including co-substrate cultivation, power-generation reinforcement, and rational metabolic engineering for improving the efficiency of C1 bioconversion are highlighted. Additionally, we updated the advances in genetic tools to manipulate methylotrophs and discussed the possible applications of methylotrophs in sustainable agriculture. We believe that upgrading methylotrophic hosts towards efficient C1-conversion is a sustainable approach to achieving C1-based industrial manufacturing.