Toxic Effects and Adaptive Response Mechanisms of Lignocellulose-Derived Phenolic Aldehydes in Saccharomyces cerevisiae during Cellulosic Ethanol Fermentation

Lignocellulose-derived phenolic aldehydes, including p-hydroxybenzaldehyde (P), vanillin (V), and syringaldehyde (S), exert synergistic inhibition on the fermentation performance of Saccharomyces cerevisiae. In this study, a robust S. cerevisiae S91 was obtained through adaptive laboratory evolution under increasing concentrations of a mixed phenolic aldehyde cocktail (P + V + S). Phenotypic analyses of S. cerevisiae S91 revealed enhanced phenolic aldehyde detoxification, improved cell morphology, and increased membrane integrity under inhibitory conditions. The evolved strain exhibited over 60% improvement in the conversion of phenolic aldehydes and demonstrated a 1.5-fold increase of ethanol titer in corn stover hydrolysate. Comprehensive transcriptomic, qRT-PCR, and fermentation evaluation revealed plasma membrane-associated genes, including GEX1 and PST2, played a vital role in the improved phenolic aldehyde tolerance of the evolved strain. This work advanced our understanding of the physiological and molecular mechanisms underlying phenolic aldehyde tolerance in S. cerevisiae and provided a robust strain for cellulosic ethanol production.