Advances in synthetic biology for engineering methylotrophic microbial cell factories

Methanol, a renewable non-food C1 substrate, holds great promise as a feedstock for sustainable biomanufacturing and carbon neutral production. However, its industrial application is hindered by low methanol assimilation efficiency in most microbes. Recent advances in synthetic biology and metabolic engineering have enabled the development of methylotrophic microbial cell factories through strategies including building efficient methanol-utilizing pathways, engineering methanol dehydrogenase for enhanced oxidation efficiency, and optimizing redox balance via cofactor utilization. Additionally, approaches such as mitigating the accumulation of toxic metabolites and adaptive laboratory evolution have been adopted to improve the robustness of synthetic methylotrophs. This review summarizes these innovations and provides a blueprint for rationally designing high-performance microbial platforms to facilitate industrial methanol utilization and advance sustainable development.