Integrated Physiological and Transcriptomic Analyses of Saccharomyces cerevisiae Under Syringaldehyde Stress

Syringaldehyde is a major lignin-derived inhibitor in lignocellulosic hydrolysates that affects growth, metabolism, and ethanol fermentation in Saccharomyces cerevisiae; however, the mechanisms underlying its toxicity and cellular adaptation remain poorly understood. In this study, fermentation analysis, physiological characterization, and transcriptomic profiling were integrated to investigate the response of S. cerevisiae to syringaldehyde stress. Syringaldehyde inhibited yeast growth and ethanol fermentation in a concentration-dependent manner. At 1.4 g/L, it caused only a minor decrease in final optical density at 560 nm (OD₅₆₀) (2.35%) but markedly decreased ethanol production and total sugar fermentation efficiency (18.65% and 17.64%, respectively), accompanied by delayed early-stage sugar utilization. Physiological analyses demonstrated that syringaldehyde induced cell-envelope alterations and induced membrane lipid peroxidation, whereas intracellular glycerol accumulation occurred only after prolonged exposure, indicating a delayed adaptive response. Transcriptome analysis identified 496 differentially expressed genes, with repression of ribosome biogenesis and cofactor biosynthesis and activation of the pentose phosphate pathway and aromatic aldehyde detoxification. Notably, ADH7, GND2, and TKL2 were strongly induced, suggesting enhanced NADPH-dependent detoxification. Collectively, these findings demonstrate that syringaldehyde induces coordinated physiological stress responses and metabolic reprogramming, including alterations in cell-envelope integrity, oxidative imbalance, and changes in fermentation-associated pathways, providing mechanistic insights into yeast adaptation to lignin-derived aromatic aldehyde stress and identifying potential targets for engineering more robust industrial yeast strains.