Differential global gene transcription of Saccharomyces cerevisiae by zinc sulfate addition under acetic acid stress and identification of novel zinc and stress-responsive genes related to cell wall function

Zinc sulfate is an important micronutrient for cell metabolism and stress protection. Acetic acid is a common inhibitor present in lignocellulosic hydrolysate, and the addition of zinc sulfate allows yeast cells to better cope with acetic acid stress. In-depth understanding of how zinc sulfate leads to changes in global gene transcription benefits efficient cellulosic ethanol production using robust yeast strains. Here, comparative transcriptomic analyses were performed using budding yeast Saccharomyces cerevisiae grown with and without zinc sulfate supplementation under acetic acid stress. Analysis showed enrichment of functions related to cell wall organization in the differentially expressed genes. Furthermore, we proved that deletion of two zinc-responsive genes, including TPS2 related to trehalose biosynthesis and CHS5 involved in protein export and chitin biosynthesis, respectively, impaired yeast growth under acetic acid stress. Meanwhile, weakened cell wall integrity of S. cerevisiae was observed by TPS2 deletion. Furthermore, overexpression of TPS2 and CHS5 exerted a positive effect on yeast growth under acetic acid stress. These results reveal a novel connection between zinc sulfate-mediated metabolic regulation and cell wall integrity, as well as provide a novel strategy for development of robust yeast strains for sustainable production of fuel ethanol and bio-based chemicals using lignocellulosic biomass.