Nitrogen starvation causes lipid remodeling in Rhodotorula toruloides

The oleaginous yeast Rhodotorula toruloides is a promising chassis organism for the biomanufacturing of value-added bioproducts. It can accumulate lipids at a high fraction of biomass. However, metabolic engineering efforts in this organism have progressed at a slower pace than those in more extensively studied yeasts. Few studies have investigated the lipid accumulation phenotype exhibited by R. toruloides under nitrogen limitation conditions. Consequently, there have been only a few studies exploiting the lipid metabolism for higher product titers. Here, we present a multi-omic investigation of the lipid accumulation phenotype under nitrogen limitation. Through an integrative lens of transcriptomic and lipidomic analysis, we identify that R. toruloides undergoes lipid remodeling during nitrogen limitation, wherein the pool of phospholipids gets remodeled to mostly storage lipids. This insight into the mechanisms of lipid accumulation can lead to the success of future metabolic engineering strategies for overproduction of oleochemicals. HighlightsO_LIThe oleaginous yeast R. toruloides displays enhanced lipid accumulation during nitrogen starvation. C_LIO_LIA multi-omic investigation of the lipid accumulation phenotype was carried out. C_LIO_LILipid remodeling was observed during the accumulation phase, wherein carbon was transferred from phospholipids to storage lipids. C_LIO_LIMulti-omic analysis suggested that selective regulation within lipid biosynthesis controls for the specific increase of storage lipids. C_LI