# Uga3 influences nitrogen metabolism in Saccharomyces cerevisiae by modulating arginine biosynthesis

## TL;DR

This study shows that Uga3, a yeast protein, affects nitrogen metabolism by indirectly regulating arginine production when proline is the only nitrogen source.

## Contribution

The paper reveals Uga3's indirect role in arginine biosynthesis and broader nitrogen regulation in yeast.

## Key findings

- Uga3 absence increases intracellular arginine levels and up-regulates ARG5,6 gene expression.
- Proteomic analysis shows Uga3 affects multiple nitrogen metabolism-related proteins.
- Uga3 does not directly bind the ARG5,6 promoter, suggesting an indirect regulatory mechanism.

## Abstract

Nitrogen metabolism in Saccharomyces cerevisiae 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 ARG5,6, a key gene in the arginine biosynthesis pathway. Proteomic analysis of uga3∆ 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 ARG5,6 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.