Microbial C1 assimilation pathways for chemical synthesis: from native metabolism to synthetic design

C1 compounds are abundant, non-food and renewable feedstocks, making them attractive substrates for producing value-added chemicals via microbial bioconversion. In nature, autotrophic microorganisms assimilate C1 substrates, including CO, CO₂, methane, methanol and formate, through native C1 fixation and assimilation pathways. Building on these natural routes, synthetic C1 assimilation pathways and engineered microbial cell factories have improved C1 utilization and broaden product portfolios. This review presents the recent progress and current strategies in producing high-value compounds using microbes possessing natural and non-natural C1 assimilation modules. We highlight key bottlenecks that limit efficient C1 assimilation and discuss potential strategies to address them, outlining opportunities for future C1-based biomanufacturing.