Systems Analysis and Engineering of Oleaginous Red Yeasts

Microbial lipids have been recognized as important renewable resources for biofuels and oleochemicals. There are some natural oleaginous yeasts capable of accumulating lipids to over 70% of their dry cell mass. In particular, the red yeast Rhodosporidium toruloides is superb for production of neutral lipids under various conditions. To understand the molecular bases of its oleaginicity, we sequenced the genome of R. toruloides and performed trans-omic analysis. Our results demonstrated that TAG accumulation under nitrogen-limited conditions is tightly connected with cellular processes related to lipogenesis, nitrogenous compounds recycling, macromolecules metabolism and autophagy. Under phosphorus-limited conditions, cells activate degradation of phosphorus-containing components including RNA and nucleic acids such as adenosine monophosphate, leading to reduced cell proliferation and enhanced lipid biosynthesis. Proteomic analysis identified 226 lipid droplet (LD)-associated proteins, and 77 of them changed abundance significantly along with lipid accumulation. The LD structural protein Ldp1 was demonstrated to facilitate giant LD formation in other yeasts. Furthermore, we have confirmed some of these data by genetic modification of R. toruloides using in-house developed tools. Taken together, our systems study revealed secrets behind yeast oleaginicity and provided rich information for engineering other cell factories.

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