Methanol metabolism in synthetic methylotrophic microorganisms

Methanol has garnered increasing attention as an ideal carbon source for chemical biomanufacturing due to its abundance and easy availability. Microbial methylotrophy mainly refers to the ability to utilize reduced one-carbon compounds such as methanol, methane or formaldehyde as sole or primary sources of carbon and energy to sustain growth. Besides native methylotrophic microbes, such as Komagataella phaffii (K. phaffii), Methylobacterium extorquens (M. extorquens), Bacillus methanolicus (B. methanolicus), many other yeasts or bacteria have been engineered to exhibit methylotrophy or by reconstructing methanol utilization pathways. This significantly broadens the scenario of methanol metabolism and leverages the well-established synthetic biology toolbox of platform microorganisms like Escherichia coli (E. coli). This article delves into the detailed examination of methanol metabolic pathways (including formaldehyde and formate) and provides an overview of recent progress in metabolic engineering for synthetic methylotrophic microorganisms. It specifically highlights the innovative C1 assimilation pathways employed in artificial methylotrophy. This comprehensive discussion aims to enhance our understanding of methanol metabolism and unlock the industrial potential of synthetic methylotrophs.