Production capacity of engineered yeast decreases due to some pressures, such as oxidative stress and protein misfolding. Results of this study showed that, the engineered yeast with enhanced mevalonate pathway, overexpression of human apoptosis regulator BCL-2 and reduced glutathione synthase GSH1 promoted the production of nerolidol by 77.7% and 32.7% in shake flasks, reached 594.1 and 446.9 mg/L, respectively. Metabolome analysis between strains with and without BCL-2 overexpression showed that there were 182 differential metabolites between these two strains. It mainly involved the metabolic pathways of fatty acids and amino acids, and biosynthetic pathways of coenzyme A and pantothenic acid. In addition, BCL-2 protein linked with endoplasmic reticulum localization signal peptide had a stronger promoting effect on nerolidol production, which was further increased by 29.2%, reaching 767.6 mg/L. This study provides an effective strategy for increasing the yield of exogenous terpenoids in engineered Saccharomyces cerevisiae.
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