Transcriptional and Physiological Responses of <i>Saccharomyces cerevisiae</i> CZ to Octanoic Acid Stress

This study elucidates the adaptive mechanisms of <i>Saccharomyces cerevisiae</i> CZ under octanoic acid stress, revealing concentration-dependent growth inhibition (76% lethality at 800 mg/L) and notable tolerance at 600 mg/L. Initial exposure (≤6 h) showed no growth impairment, but prolonged treatment induced dose-dependent lethality, accompanied by reduced H⁺/K⁺-ATPase activity and elevated malondialdehyde (MDA) levels, indicative of oxidative damage. Transcriptomic profiling of 5665 genes highlighted the predominant downregulation of ribosomal functions (translation, ribosome biogenesis) and amino acid metabolism pathways (e.g., <i>ARO10</i>, <i>ARO9</i>). Strain-specific regulatory dynamics were observed: (1) <i>TPO1</i>-mediated efflux was active at 400 mg/L but absent at 600 mg/L, suggesting compensatory mechanisms under high stress; (2) <i>HTX1</i>-related genes exhibited bidirectional regulation (downregulated at 400 mg/L vs. upregulated at 600 mg/L), reflecting metabolic flexibility; (3) <i>ACC1</i> downregulation (600 mg/L) and unaltered <i>SFK1</i> expression contrasted with lipid-remodeling strategies in engineered strains; and (4) <i>PMA2</i> suppression diverged from literature-reported <i>PMA1</i> activation, underscoring strain-specific energy reallocation. Suppression of ergosterol biosynthesis and ribosomal genes revealed a trade-off between stress adaptation and biosynthetic processes. These findings reconcile prior contradictions by attributing discrepancies to genetic backgrounds (CZ vs. laboratory/engineered strains) and methodological variations. Unlike strains relying on phospholipid asymmetry or oleic acid overproduction, CZ’s unique tolerance stems from integrated membrane homeostasis (via lipid balance) and metabolic conservation. This work emphasizes the critical role of strain-specific regulatory networks in octanoic acid resistance and provides insights for optimizing yeast robustness through targeted engineering of membrane stability and metabolic adaptability. Future studies should employ multi-omics integration to unravel the dynamic gene regulatory logic underlying these adaptive traits.