Abstract: The metabolic mechanism of Saccharomyces cerevisiae in response to formic acid stress was studied by non-targeted metabolomics based on liquid chromatography-mass spectrometry (LC-MS) in this work. The data were analyzed by multivariable statistical methods such as principal component analysis (PCA) and orthogonal partial least squares discriminate analysis (OPLS-DA). Totally 226 significantly differential metabolites (P < 0.05) with a variable importance in the projection (VIP) value greater than 1 were identified in Saccharomyces cerevisiae under formic acid stress, mainly including L-tryptophan, L-glutamine, 5-hydroxyindoleacetic acid, indoleacetaldehyde, L-phenylalanine, L-glutamate, oxidized glutathione, and 5’-phosphoribosyl-N-formylglycinamide. The analysis of differential metabolic pathways showed that formic acid stress may cause reactive oxygen species (ROS) accumulation, inducing oxidative stress and excessive ATP consumption, and ultimately inhibiting yeast cell growth. In addition, by increasing the contents of intracellular aromatic amino acids and slowing down the rate of anabolism of some amino acids and nucleotides to reduce energy consumption, yeast cells could protect themselves, thus contributing to the improvement of their tolerance to formic acid. This study provides a scientific theoretical reference for further research on methods to improve cellular tolerance to acid inhibitors.

Key words: Saccharomyces cerevisiae; formic acid stress; non-targeted metabolomics