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To improve cellulosic ethanol yield and develop the cost-effective simultaneous saccharification fermentation for ethanol production,the strain should be developed with improved tolerance to high temperature and inhibitory compounds from lignocellusic biomass.Here,an industrial strain of S.cerevisiae Ethanol Red E491 (Ethanol Performance Group,NJ,USA) was evolved using corn cob hydrolyzate at stepincreased temperature (from 37-45℃) and the resulting daughter strain,TIB-S.C Y45,produced ethanol much more rapidly than its parent in fermentations of corn cob hydrolyzate at 40℃-45℃.Adaptation improved fermentation performance of the evolved strain.Based on differential integrative omic analysis,we find evidence of parallel evolution in many genes.Consistent with the complex,multigenic nature of multiplestresses,we observe adaptations in a diversity of cellular processes.Many adaptations appear to involve epistasis between different mutations,implying a rugged fitness landscape for the tolerance of high temperature and inhibitory compounds in yeast.