Enhanced tolerance of Saccharomyces cerevisiae to industrial inhibitors through multi-transcription factor engineering for environmental and biotechnological applications

This study presents a novel approach to enhance the tolerance of Saccharomyces cerevisiae to industrial inhibitors, including furfural, 5-hydroxymethylfurfural (HMF), acetic acid, formic acid, anhydrous ethanol, and phenol. By co-overexpressing the transcription factors PDR1, YAP1 , and RPN4, engineered yeast strains exhibited significantly improved stress resistance , with shorter lag phases and higher growth rates compared to parental strains. RNA sequencing revealed upregulation of key genes involved in NADPH regeneration, redox balance, and cell membrane stabilization , while downregulation of protein modification genes suggested an energy-efficient oxidative stress management strategy. These findings demonstrate the potential of multi-transcription factor engineering to improve yeast strain performance under toxic conditions, with important implications for industrial bioethanol production and environmental pollutant degradation. Future research should focus on optimizing these strains for broader industrial applications, including scaling up fermentation processes to enhance bioethanol yield and environmental remediation. • Enhanced Saccharomyces cerevisiae tolerance to furfural and multiple industrial inhibitors. • Co-overexpression of PDR1, YAP1, and RPN4 transcription factors significantly improved stress resistance. • RNA sequencing revealed key pathways for NADPH regeneration and redox balance enhancement. • Energy-efficient oxidative stress management was achieved by downregulating protein modification genes. • Potential applications include improved bioethanol production and environmental pollutant remediation.