Coarse-Grained Modeling Elucidates Differential Metabolism of <i>Saccharomyces cerevisiae</i> under Varied Nutrient Limitations

Microorganisms such as <i>Saccharomyces cerevisiae</i> have a native ability to adapt their metabolism to varying nutrient conditions. Understanding their responses to nutrient limitations is critical for decoding cellular physiology and designing strategies for metabolic engineering. While the influence of carbon availability on yeast metabolism has been extensively studied, the role of nitrogen availability remains relatively underexplored. In this study, we utilized a coarse-grained kinetic model to systematically analyze and compare the effects of carbon and nitrogen limitations on yeast metabolism. Our model successfully revealed the differential metabolic characteristics of <i>S. cerevisiae</i> under carbon- and nitrogen-limited chemostat conditions. It also highlighted the significance of protein activity regulation at varying carbon-to-nitrogen ratios, and elucidated distinct strategies employed to maintain ATP homeostasis. This study provides a computational tool for investigating yeast physiology under nutrient limitations and offers quantitative and mechanistic insights into yeast metabolism.