On June 25, the research team led by Professor Han Shuangyan at SCUT achieved a major breakthrough in synthetic biology.Relevant findings were published in Nature Synthesis under the title Membrane remodelling for increased methanol tolerance in Komagataella phaffii. By engineering the glycerophospholipid metabolic pathway of Komagataella phaffii, the team developed S33, an engineered strain with methanol tolerance exceeding 10%, setting a new global record for microbial methanol tolerance.

Methanol, a renewable C1 feedstock produced from carbon dioxide and biomass, serves as an alternative to food-based carbon sources. However, high methanol concentrations often disrupt microbial cell membranes and trigger oxidative damage. Conventional strains only withstand methanol concentrations up to 1%–5%, failing to meet the stringent requirements of industrial fermentation. This research team elucidated the death mechanisms of yeast under methanol stress, and confirmed that cell membrane homeostasis is one key factor for enhancing methanol tolerance. By simultaneously overexpressing four critical genes—PET2, PSA, 0178, and 0267—they successfully constructed strain S33 .

S33 exhibits stable tolerance to methanol concentrations of 10%-13%, with  the maximum one-time methanol dosage reaching 16% in a single fermentation. High methanol concentrations suppress contaminants, eliminating the need for rigorous sterilization. It yields lipids at 40 g/L, accounting for 40% of cell dry weight, with great industrial prospects. This study proposed, for the first time, the theoretical model of membrane lipid remodelling-driven metabolic reprogramming,”revolutionizing the approach to methanol tolerance engineering. It delivers theoretical and technical frameworks for robust microbial cell factories, accelerates the industrialization of one-carbon biorefining , and supports China’s dual carbon goals and green manufacturing strategy.