초록
<P>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.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Synthetic methylotrophy, which integrates natural or artificial methanol assimilation pathways in platform microorganisms, can be exploited to produce fuels and chemicals using methanol as a feedstock. </LI> <LI> Enzyme engineering strategies, including enzyme mining, directed evaluation, and construction of multifunctional enzyme complexes, are being applied to overcome the rate-limiting steps of methanol bioconversion. </LI> <LI> Metabolic engineering approaches guided by systems and synthetic biology, including <I>in silico</I> pathway design and construction of synthetic methanol-dependent strains, are being used to enhance methanol utilization. </LI> <LI> Recent advances in bioproduction using synthetic methylotrophs are expanding the portfolio of products that can be produced from methanol. </LI> </UL> </P>