Nitrogen limitation causes a seismic shift in redox state and phosphorylation of proteins implicated in carbon flux and lipidome remodeling in Rhodotorula toruloides

作者：Austin Gluth, Jeffrey J. Czajka, Xiaolu Li, Kent Bloodsworth, Josie Eder, Jennifer E. Kyle, Rosalie Chu, Bin Yang, Weijun Qian, Pavlo Bohutskyi, Tong Zhang · 发表于：Biotechnology for Biofuels and Bioproducts · 年份：2025 · DOI：10.1186/s13068-025-02657-y · 被引用次数：9 · 研究领域：Lipid metabolism and biosynthesis、Microbial Metabolic Engineering and Bioproduction、Metabolomics and Mass Spectrometry Studies

BACKGROUND: Oleaginous yeast are prodigious producers of oleochemicals, offering alternative and secure sources for applications in foodstuff, skincare, biofuels, and bioplastics. Nitrogen starvation is the primary strategy used to induce oil accumulation in oleaginous yeast as part of a global stress response. While research has demonstrated that post-translational modifications (PTMs), including phosphorylation and protein cysteine thiol oxidation (redox PTMs), are involved in signaling pathways that regulate stress responses in metazoa and algae, their role in oleaginous yeast remain understudied and unexplored. RESULTS: Towards linking the yeast oleaginous phenotype to protein function, we integrated lipidomics, redox proteomics, and phosphoproteomics to investigate Rhodotorula toruloides under nitrogen-rich and starved conditions over time. Our lipidomics results unearthed interactions involving sphingolipids and cardiolipins with ER stress and mitophagy. Our redox and phosphoproteomics data highlighted the roles of the AMPK, TOR, and calcium signaling pathways in regulation of lipogenesis, autophagy, and oxidative stress response. As a first, we also demonstrated that lipogenic enzymes including fatty acid synthase are modified as a consequence of shifts in cellular redox states due to nutrient availability. CONCLUSIONS: We conclude that lipid accumulation is largely a consequence of carbon rerouting and autophagy governed by changes to PTMs, and not increases in the ab...