Synthetic Methylotrophy: A Practical Solution for Methanol-Based Biomanufacturing

The increasing availability and affordability of natural gas has renewed interest in using methanol for bioproduction of useful chemicals. Engineering synthetic methylotrophy based on natural or artificial methanol assimilation pathways and genetically tractable platform microorganisms for methanol-based biomanufacturing is drawing particular attention. Recently, intensive efforts have been devoted to demonstrating the feasibility and improving the efficiency of synthetic methylotrophy. Various fuel, bulk, and fine chemicals have been synthesized using methanol as a feedstock. However, fully synthetic methylotrophs utilizing methanol as the sole carbon source and commercially viable bioproduction from methanol remain to be developed. Here, we review ongoing efforts to identify limiting factors, optimize synthetic methylotrophs, and implement methanol-based biomanufacturing. Future challenges and prospects are also discussed.