Metabolic adaptations of yeast cells to epigenetic modifiers: a comparative analysis of free amino acid profiles and key metabolites.

This study investigates the effects of four epigenetic treatments on the free amino-acid and central-carbon metabolite profiles of Saccharomyces cerevisiae. The objective was to assess how naturally derived epigenetic agents reshape yeast metabolism, with a particular focus on amino-acid pools and key intermediates of glycolysis and the tricarboxylic acid (TCA) cycle. Yeast cultures were grown in media supplemented with 5-azacytidine, sodium butyrate, curcumin, or green tea extract, and metabolites were quantified using LC-MS/MS. All four treatments induced marked shifts in amino-acid abundance. Essential amino acids-including leucine, tryptophan, and phenylalanine-significantly increased, with azacytidine yielding the strongest elevation (up to two-fold relative to control). Non-essential amino acids showed similar upward trends across treatments. Central-carbon metabolites such as pyruvate, acetyl-CoA, and citrate also accumulated substantially. Correlation-based and network analyses revealed coordinated modules linking amino-acid metabolism with energy-producing pathways, and enrichment analysis highlighted perturbations in gluconeogenesis and fatty-acid metabolism. Collectively, these results provide a quantitative and network-level perspective on metabolic reorganization induced by epigenetic modulators and establish a reference framework for future multi-omics investigations in yeast.