Improved methanol utilization of Komagataella phaffii by rebuilding metabolic network based on new alcohol-aldehyde transformation system.

Bioconversion based on methanol holds promise for advancing global carbon neutrality and mitigating the global food crisis. However, the limited efficiency of methanol utilization hampers methanol-based biomanufacturing in microorganisms. This study focuses on enhancing methanol utilization efficiency in Komagataella phaffii through the implementation of a novel alcohol-aldehyde conversion system based on the Adh900 protein. Results indicate a notable 14 % increase in biomass compared to the wild-type strain. Furthermore, analysis of the amino acid metabolism pathway underscores the significance of histidine in facilitating the methanol utilization pathway (MUTP). By combination of adding 120 mg/L histidine to the medium and optimizing promoter strategies, the dry cell weight (DCW) was up to 4.33 g DCW/L, which was increased by 63 %. The combination of these strategies has important research significance for methanol-based biological metabolism, and will further promote the microbial application of methanol. These findings are poised to advance the development of methanol-nutritive cell factories, thereby propelling the evolution of methanol biomanufacturing technology.