Genotype-by-environment-by-environment interactions in the Saccharomyces cerevisiae transcriptomic response to alcohols and anaerobiosis

Next generation biofuels including longer-chain alcohols such as butanol are attractive as renewable, high-energy fuels. A barrier to microbial production of butanols is the increased toxicity compared to ethanol; however, the cellular targets and microbial defense mechanisms remain poorly understood, especially under anaerobic conditions used frequently in industry. Here we took a comparative approach to understand the response of Saccharomyces cerevisiae to 1-butanol, isobutanol, or ethanol, across three genetic backgrounds of varying tolerance in aerobic and anaerobic conditions. We find that strains have different growth properties and alcohol tolerances with and without oxygen availability, as well as unique and common responses to each of the three alcohols. Our results provide evidence for strain-by-alcohol-by-oxygen interactions that moderate how cells respond to alcohol stress.\n\nARTICLE SUMMARYEfforts to promote sustainable bioenergy focus on microbial production of biofuels including butanols, which can be blended into gasoline engines and condensed for higher energy fuels. The stress of these end products can limit microbial production; yet it remains unclear how higher-energy butanols impact cell physiology compared to the well studied ethanol. This study compares the transcriptomic response to 1-butaonol, isobutanol, and ethanol in three strains of Saccharomyces cerevisiae from diverse natural populations, with and without oxygen. Results show that oxygen availability and strain background significantly impact the response to each alcohol and point to shared responses to alcohol stress.