Metabolomic study of interactive effects of phenol, furfural, and acetic acid on Saccharomyces cerevisiae

Metabolic profiling was carried out to investigate the interactive effects of three representative inhibitors (furfural, phenol, and acetic acid) in lignocellulosic hydrolysate on Saccharomyces cerevisiae during ethanol fermentation. Our results revealed that three inhibitors exhibited significantly synergistic effects on the growth, fermentation, and some metabolites of yeast. Acetic acid exerted the most severe effects on yeast in the combination of three inhibitors, enhancing amino acids metabolism and inhibiting central carbon metabolism. The effects on yeast cells by acetic acid were enhanced by the presence of phenol and furfural, which might be owing to the loss of membrane integrity and the inhibition on metabolism. Further investigation indicated that the combination of inhibitors also exhibited antagonistic effects mainly on threonine, cadaverine, inositol, and tryptophan, weakening or reversing the effects of individual inhibitor. It might be due to the more severe damage by the combined inhibitors, and different repairing mechanism of cells in the presence of individual and combined inhibitors. Better understanding of the synergistic and antagonistic effects of the inhibitors will be helpful for the improvement of tolerant strains and the optimization of lignocellulosic fermentation.