RkMsn4, a zinc finger transcription factor, regulates carotenoid and lipid metabolism to enhance tolerance to environmental stress in Rhodosporidium kratochvilovae.

Red yeasts serve as indispensable microbial resources for the production of carotenoids and lipids; however, environmental stress factors often limit their performance during industrial fermentation. The zinc-finger transcription factors Msn2/Msn4 act as central regulators of stress responses in yeasts. However, researchers have not yet systematically elucidated the similarities and differences in the mechanisms underlying the regulatory effects of Msn2/Msn4 under different stress conditions. In this study, we compared the shared and stress-specific regulatory functions of RkMsn4 in Rhodosporidium kratochvilovae YM25235 under conditions of glucose starvation, 15 °C low temperature, and 4% NaCl salt stress. RkMsn4 contributed to the activity of the oxidative defense systems, including antioxidant enzymes, carotenoids, and glutathione, and the remodeling of membrane lipids, including phospholipids and unsaturated fatty acids (UFAs) across all three stress conditions. Additionally, RkMsn4 regulated stress-specific metabolic regulation by modulating branched-chain amino acid (BCAA) and aromatic amino acid (AAA) metabolism under glucose starvation conditions and promoting the utilization of exogenous sucrose and fructose under salt stress. By conducting weighted gene co-expression network analysis (WGCNA), we identified candidate genes potentially associated with carotenoid and lipid metabolism. These findings provide practical insights for improving tolerance to stress and metabolic productivity of red yeasts in industrial bioprocesses.IMPORTANCERed yeasts are important microorganisms for the production of carotenoids and lipids, but their performance is often limited by environmental stress. Understanding how red yeasts respond to environmental stress is crucial for advancing their application in industrial fermentation. This study reveals the stress response mechanisms mediated by the transcription factor RkMsn4 in Rhodosporidium kratochvilovae YM25235 under glucose starvation, low temperature, and salt stress, as well as its regulatory role in carotenoid and lipid metabolism. These findings provide valuable insights for enhancing the stress resistance and productivity of red yeasts in industrial applications.