Metabolome analysis of the response and tolerance mechanisms of Saccharomyces cerevisiae to formic acid stress

Various inhibitors are produced during the hydrolysis of lignocellulosic biomass that can interfere with the growth of yeast cells and the production of bioethanol. Formic acid is a common weak acid inhibitor present in lignocellulosic hydrolysate that has toxic effects on yeast cells. However, the mechanism of the response of Saccharomyces cerevisiae to formic acid is not fully understood. In this study, liquid chromatography-mass spectrometry (LC-MS) was used to investigate the effects of formic acid treatment on cell metabolites of S. cerevisiae. Treatment with different concentrations of formic acid significantly inhibited the growth of yeast cells, reduced the yield of ethanol, prolonged the cell fermentation cycle, and increased the content of malondialdehyde. Principal component analysis and orthogonal partial least squares discriminant analysis showed that 55 metabolites were significantly altered in S. cerevisiae after formic acid treatment. The metabolic relevance of these compounds in the response of S. cerevisiae to formic acid stress was investigated. Formic acid can cause oxidative stress, inhibit protein synthesis, and damage DNA in S. cerevisiae, and these are possible reasons for the inhibition of S. cerevisiae cell growth. In addition, the levels of several aromatic amino acids identified in the cells of formic acid-treated yeast were increased; the biosynthesis of nucleotides was slowed, and energy consumption was reduced. These mechanisms may help to improve the tolerance of yeast cells to formic acid. The results described herein highlight our current understanding of the molecular mechanism of the response of S. cerevisiae to formic acid. The study will provide a theoretical basis for research on the tolerance mechanisms of S. cerevisiae.