Engineering the native methylotrophs for the bioconversion of methanol to value-added chemicals: current status and future perspectives

Methanol is becoming an attractive fermentation feedstock for large-scale bioproduction of chemicals, due to its natural abundance and mature production technology. Native methylotrophs, which can utilize methanol as the only source of carbon and energy, are ideal hosts for methanol bioconversion due to their high methanol utilization rate and have been extensively employed in the production of value-added chemicals from methanol. Here, we review the natural methanol utilization pathways in native methylotrophs, describing the available synthetic biology tools developed for engineering native methylotrophs, and discuss the strategies for improving their methanol utilization efficiency. Finally, the representative examples of engineering the native methylotrophs to produce value-added products from methanol are summarized. Furthermore, we also discuss the major challenges and possible solutions for the application of native methylotrophs in methanol-based biomanufacturing.