Construction and applications of methanol bio-converting cell factories

Methanol is a highly promising feedstock for biomanufacturing owing to its broad availability, low cost, and high energy density. Methylotrophic fermentations have been exploited to produce diverse fuels, chemicals, and materials. However, although such processes have been practiced for decades, their applications have been constrained by low methanol assimilation efficiency, insufficient cellular energy and reducing equivalents supply, the cytotoxicity of methanol and its intermediates, and inadequate robustness of chassis strains. In this review, progress is synthesized along four pillars for constructing high-performance methanol bio-converting cell factories: methanol assimilation pathways, energy-supply strategies, tolerance-enhancement approaches, and metabolic engineering for chemical synthesis, with the aim of informing the rational design and construction of efficient methanol bio-converting cell factories.