Metabolic Regulation Mechanism Underlying Efficient Astaxanthin Accumulation in Phaffia rhodozyma Induced by Titanium Dioxide Stress

In this study, the metabolic mechanism underlying the efficient accumulation of astaxanthin in Phaffia rhodozyma PR106 induced by titanium dioxide (TiO₂) stress was investigated by the combined use of untargeted metabolomics and microscopic observation. Metabolomic analysis revealed that TiO₂ stress significantly changed intracellular metabolites closely linked to astaxanthin biosynthesis in PR106 cells, such as sucrose, 5-dehydroepisterol, and (6Z)-octadecenoic acid, which were downregulated after 16 h and upregulated after 32 h. Furthermore, TiO₂ stress promoted astaxanthin synthesis by regulating key metabolic pathways, including ABC transporters, the phosphotransferase system, steroid biosynthesis, and amino acid biosynthesis, which were highly consistent with the major metabolic pathway changes observed during astaxanthin accumulation in PR106. In addition, TiO₂ stress reduced cell wall permeability, enhanced membrane fluidity, and increased the number of lipid droplets and mitochondria. This study provides a theoretical basis for rational redesign of P. rhodozyma based on the metabolic mechanism to enhance astaxanthin accumulation, thus helping to achieve efficient astaxanthin production by P. rhodozyma.