Uga3 influences nitrogen metabolism in Saccharomyces cerevisiae by modulating arginine biosynthesis

Authors:

Nicolás Urtasun1,2,a, Sebastián Aníbal Muñoz1,a, Martín Arán3 and Mariana Bermúdez-Moretti1
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Affiliations:

1 Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento Química Biológica. Buenos Aires, Argentina – CONICET. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN). Buenos Aires, Argentina. 2 Departamento de Ciencias Básicas y Experimentales, Universidad Nacional del Noroeste de La Provincia de Buenos Aires (UNNOBA), Junín, Buenos Aires, Argentina. 3 Fundación Instituto Leloir e Instituto de Investigaciones Bioquímicas de Buenos Aires (IIBBA) – CONICET, Patricias Argentinas 435 (C1405BWE), Buenos Aires, Argentina.

a These authors contributed equally to this work.

Keywords: 

nitrogen metabolism, proline catabolism, arginine biosynthesis, Saccharomyces cerevisiae, Uga3 transcription factor.

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Corresponding Author(s):

Mariana Bermúdez-Moretti, Departamento de Química Biológica, IQUIBICEN-CONICET, Facultad Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, Buenos Aires 1428, Argentina; mariana@qb.fcen.uba.ar

Conflict of interest statement:

The authors declare that no competing interests exist.

Please cite this article as:

Nicolás Urtasun, Sebastián Aníbal Muñoz, Martín Arán and Mariana Bermúdez-Moretti (2025). Uga3 influences nitrogen metabo-lism in Saccharomyces cerevisiae by modulating arginine biosynthesis. Microbial Cell 12: 132-140. doi: 10.15698/mic2025.06.851

© 2025 Urtasun et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestrict-ed use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.

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.

doi: 10.15698/mic2025.06.851
Volume 12, pp. 132 to 140, published 12/06/2025.