Roles of the Yap1 Transcription Factor and Antioxidants in Saccharomyces cerevisiae's Tolerance to Furfural and 5-Hydroxymethylfurfural, Which Function as Thiol-Reactive Electrophiles Generating Oxidative Stress

Abstract

Development of the tolerance of Saccharomyces cerevisiae strains to furfural and 5-hydroxymethylfurfural (HMF) is an important issue for cellulosic ethanol production. Although furfural and HMF are known to induce oxidative stress, the underlying mechanisms are largely unknown. In this study, we show that both furfural and HMF act as thiol-reactive electrophiles, thus directly activating the Yap1 transcription factor via the H 2 O 2 -independent pathway, depleting cellular glutathione (GSH) levels, and accumulating reactive oxygen species in Saccharomyces cerevisiae. However, furfural showed higher reactivity than did HMF toward GSH in vitro and in vivo. In line with such toxic mechanisms, overexpression of YAP1 C620F , a constitutively active mutant of YAP1, and Yap1 target genes encoding catalases (CTA1 and CTT1) increased tolerance to furfural and HMF. However, increasing GSH levels by overexpression of genes for GSH biosynthesis (GSH1 and GLR1) or by the exogenous addition of GSH to the culture medium enhanced tolerance to furfural but not to HMF.

Use of Lignocellulosic Materials for PHA Production

“…One possible mechanism is that phenolics interfere with the cell membrane by influencing its function and changing its protein-to-lipid ratio. Phenolic compounds are also investigated with regard to inhibition of enzymatic hydrolysis of cellulose; experiments with phenols suggest that one way in which they affect proteins is by inducing precipitation 21 .…”

Understanding the Mechanism of Thermotolerance Distinct From Heat Shock Response Through Proteomic Analysis of Industrial Strains of Saccharomyces cerevisiae

“…Msn2/4 activation is known to trigger a so-called environmental stress response so as to adapt yeast cells to various adverse conditions including ethanol, heat shock, chemical toxic, osmotic stress, and oxidative stress (15,61). Yap1 mainly regulating oxidative stress response and redox homeostasis was also expected to be the major player in HSR due to the well-recognized intersection between heat shock stress and oxidant defense (62). Disappearance of Msn4 and Yap1 from the top 10 TF list for TR suggested thermotolerant strains may rely more on heat stress-specific regulatory mechanism rather than initiating general stress responses or oxidative defense.…”

Polyamine Transporters and Polyamines Increase Furfural Tolerance during Xylose Fermentation with Ethanologenic Escherichia coli Strain LY180

“…Genes have been described that increase the resistance of bacterial and yeast biocatalysts to furfural and hydroxymethylfurfural (5,7,(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). However, to date, none have completely solved the toxicity problem.…”

“…However, to date, none have completely solved the toxicity problem. In Saccharomyces cerevisiae, overexpression of the transcription factor Yap1 has been shown to increase tolerance to both furfural and HMF (17). Disruption of pentose phosphate pathway (PPP) genes (ZWF1, GND1, RPE1, and TKL1) led to increased sensitivity to furfural and HMF in S. cerevisiae (10).…”