Uga3 influences nitrogen metabolism in Saccharomyces cerevisiae by modulating arginine biosynthesis

Abstract

ABSTRACT Nitrogen metabolism in Saccharomyces cerevisiae is tightlyregulated to optimize the utilization of available nitrogen sources. Uga3 is aknown transcription factor involved in the gamma-aminobut yric acid (GABA)pathway; however, its broader role in nitrogen metabolism remains unclear. Here, we demonstrate that Uga3 influences arginine biosynt hesis, linki ng itsfunction beyond GABA utilization when cells grow with proline as the soleand poor nitrogen source. Using a combination of intracellular amino acidquantification, proteomics, and gene expression analysi s, we show that theabsence of Uga3 leads to a significant increase in intracellular arginine levelsand the up-regulation of ARG5,6, a key gene in the arginine biosynthesi spathway. Proteomic analysis of uga3∆ cells reveals differential expression ofmultiple nitrogen metabolism- related proteins, suggesting a broader regul atoryrole for Uga3. Surprisingly, chromatin i mmunopreci pitati on (ChIP) assaysindicate that Uga3 does not directly bind the ARG5, 6 promoter, implying anindirect regulatory mechanism. These findings expand the known functionsof Uga3, positioning it as a key player in the coordinated regulation of nitrogenmetabolism. Given the impact of nitrogen availability on industrial fermentationprocesses, our results provide new insights into optimizing yeastperformance under nitrogen-limited conditions.