PNNL

Abstract

Oleaginous yeast are prodigious producers of oleochemicals, offering sustainable sources for applications in foodstuff, skincare, biofuels, and bioplastics. Nitrogen starvation is the primary strategy used to induce oil accumulation as part of a global stress response. While research has demonstrated that protein thiol oxidation (redox PTMs) is involved in signaling pathways that regulate stress response in metazoa and algae, its role in oleaginous yeast remains unexplored. 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. 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 and oxidative stress response. This work provides putative PTM switches that could enable advanced metabolic engineering strategies to decouple lipid accumulation from nitrogen limitation.