Chromosome III aneuploidy enhances ethanol tolerance in industrial Saccharomyces cerevisiae by increasing TUP1 expression

Ethanol stress poses a considerable challenge for Saccharomyces cerevisiae during fermentation. Strains carrying an extra copy of chromosome III exhibit enhanced ethanol tolerance. Here, we investigated the underlying mechanisms of this tolerance, focusing on gene dosage effects and differential gene expression under ethanol stress. We compared the gene expression profiles of a strain with three copies of chromosome III and its derivative with two copies, exposed to 6% and 10% ethanol. Our analysis identified TUP1 , located on chromosome III, as a key regulator of the ethanol stress response. Deleting one copy of TUP1 in the tolerant strain diminished its ethanol tolerance, suggesting that chromosome III aneuploidy in ethanol-tolerant strains enhances adaptive responses by increasing TUP1 copy number. Our findings offer insights into the genetic basis of ethanol tolerance, with potential applications for optimizing industrial fermentation processes and understanding the role of aneuploidy in the domestication of industrial yeasts.