Engineering Saccharomyces cerevisiae to Enhance Fatty Acid Production via Formate Electrolytes

Fossil fuel overuse drives excessive CO2emissions, exacerbating environmental degradation and climate change. Coupling electrochemistry with microbial fermentation provides a promising route to convert CO2into fuels and chemicals. However, microbial electrolytic solution tolerance remains a critical bottleneck, as observed in model organisms likeSaccharomyces cerevisiae(S. cerevisiae). To address this, we engineeredS. cerevisiaeto utilize electrochemically derived formate, thereby boosting free fatty acids (FFAs) production. By optimizing culture conditions and heterologously expressing formate dehydrogenase (FDH), we improved formate assimilation efficiency. Additionally, we introduced stress-resistant genes for a better electrolytic solution tolerance to sustain growth and FFAs synthesis under harsh electrolytic conditions (e.g., high formate/salt ion concentrations), eliminating the need to separate formate from the electrolyte post-electrolysis. In the presence of 4 g/L formate electrolytic medium, the engineered strain YB061 achieved a 41.9% increase in biomass and a formate conversion rate exceeding 97.0%. Compared to the parental strain, YB061 enhanced FFAs production by 92.8% by utilizing formate-containing electrolytes, demonstrating great potential for bio-electrochemical manufacturing. However, further work is needed to improve yeast tolerance to high formate concentrations and to enable direct coupling of CO2electroreduction with microbial cultivation.