Epigenetic regulation of metabolism in Saccharomyces cerevisiae: mechanisms, metabolic crosstalk, and engineering applications.

Epigenetic regulation plays a central role in metabolic gene expression in eukaryotes. Focusing on Saccharomyces cerevisiae as a model, this review systematically examines how histone modifications, including acetylation, methylation, phosphorylation, ubiquitination, and SUMOylation, and ATP‑dependent chromatin remodeling regulate metabolic genes. It also summarizes the crosstalk between metabolic signals and epigenetic states. On this basis, practical progress, advantages, and limitations of applying these mechanisms in metabolic engineering are then discussed, including industrial strain optimization and the development of epigenetic molecular tools, as well as their technical limitations and scale-up challenges. In addition, yeast models for human diseases are introduced, covering tumor-associated histone dysregulation and antifungal drug resistance. Future research should focus on elucidating the dynamic and combinatorial mechanisms of epigenetic regulation, the direct regulation of chromatin remodeling complexes by metabolic signals, and the development of more precise and stable regulatory strategies. These findings provide insights into metabolic regulation in higher eukaryotes and lay a foundation for industrial biotechnology, synthetic biology, and disease research.