Engineering <i>Saccharomyces cerevisiae</i> to Enhance Fatty Acid Production via Formate Electrolytes

Fossil fuel overuse drives excessive CO₂ emissions, exacerbating environmental degradation and climate change. Coupling electrochemistry with microbial fermentation provides a promising route to convert CO₂ into fuels and chemicals. However, microbial electrolytic solution tolerance remains a critical bottleneck, as observed in model organisms like <i>Saccharomyces cerevisiae</i> (<i>S. cerevisiae</i>). To address this, we engineered <i>S. cerevisiae</i> to 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 CO₂ electroreduction with microbial cultivation.