A CRISPR Interference Screen of Essential Genes Reveals that Proteasome Regulation Dictates Acetic Acid Tolerance in Saccharomyces cerevisiae
Vaskar Mukherjee, Ulrika Lind, Robert P. St.Onge, Anders Blomberg, Yvonne Nygård
Abstract
Acetic acid is inhibitory to the growth of the yeast Saccharomyces cerevisiae, causing ATP starvation and oxidative stress, which leads to the suboptimal production of fuels and chemicals from lignocellulosic biomass. In this study, where each strain of a CRISPRi library was characterized individually, many essential and respiratory growth-essential genes that regulate tolerance to acetic acid were identified, providing a new understanding of the stress response of yeast and new targets for the bioengineering of industrial yeast. Our findings on the fine-tuning of the expression of proteasomal genes leading to increased tolerance to acetic acid suggest that this could be a novel strategy for increasing stress tolerance, leading to improved strains for the production of biobased chemicals.