Uga3 influences nitrogen metabolism in Saccharomyces cerevisiae by modulating arginine biosynthesis

Nitrogen metabolism in <i>Saccharomyces cerevisiae</i> is tightly regulated to optimize the utilization of available nitrogen sources. Uga3 is a known transcription factor involved in the gamma-aminobutyric acid (GABA) pathway; however, its broader role in nitrogen metabolism remains unclear. Here, we demonstrate that Uga3 influences arginine biosynthesis, linking its function beyond GABA utilization when cells grow with proline as the sole and poor nitrogen source. Using a combination of intracellular amino acid quantification, proteomics, and gene expression analysis, we show that the absence of Uga3 leads to a significant increase in intracellular arginine levels and the up-regulation of <i>ARG5,6</i>, a key gene in the arginine biosynthesis pathway. Proteomic analysis of <i>uga3</i>∆ cells reveals differential expression of multiple nitrogen metabolism-related proteins, suggesting a broader regulatory role for Uga3. Surprisingly, chromatin immunoprecipitation (ChIP) assays indicate that Uga3 does not directly bind the <i>ARG5,6</i> promoter, implying an indirect regulatory mechanism. These findings expand the known functions of Uga3, positioning it as a key player in the coordinated regulation of nitrogen metabolism. Given the impact of nitrogen availability on industrial fermentation processes, our results provide new insights into optimizing yeast performance under nitrogen-limited conditions.