Multi‐Omics Analysis Reveals the Selenium‐Regulatory Metabolism in Rare Yeast <i>Kazachstania unispora</i> KU2

ABSTRACT Selenium (Se)‐enriched yeast is the best Se source to address Se deficiency–related health issues. Kazachstania unispora ( K. unispora ) is a rare yeast that effectively bioaccumulates organic Se. However, the Se enrichment mechanism of K. unispora remains poorly characterized. This study explored the characteristic differences between Se‐enriched K. unispora KU2 and non‐enriched counterpart via integrated genomics, transcriptomics, and metabolomics analysis. A total of 138 metabolites and 1561 genes exhibited significant alternations during Se enrichment. Joint analysis revealed unique Se‐regulatory pathways, predominately arginine biosynthesis, the TCA cycle, glutathione metabolism, and selenocompound metabolism. Among them, seven differentially expressed genes, including glnA , E1.2.1.88 , DLD , acnA , GPT , metH , and CTH , were identified as key Se‐regulatory genes in K. unispora KU2. These findings provide useful knowledge for targeting Se levels in K. unispora and new insights into commercial application of K. unispora as a probiotic to promote human health.