Global transcriptome profiling reveals genes responding to overproduction of a small secretory, a high cysteine- and a high glycosylation-bearing protein in Yarrowia lipolytica

Investigation of the yeast cell’s response to recombinant secretory protein (rs-Prot) overproduction is relevant for both basic and applied research. Imbalance, overloading or stress within this process impacts the whole cell. In the present study, by using steady-state cultures and transcriptomics, we investigated the cellular response of Yarrowia lipolytica challenged with high-level expression of genes encoding proteins with significantly different biochemical characteristics: a small protein retained within the cell i) or secreted ii), a medium size secretory protein with a high number of disulfide bonds iii), or glycosylation sites iv). Extensive analysis of omics data, supported by careful manual curation, led to some anticipated observations on oxidative and unfolded protein stress (CTT1, PXMP2/4, HAC1), glycosylation (ALGs, KTRs, MNTs, MNNs), folding and translocation (SSAs, SSEs) but also generated new exciting knowledge on non-conventional protein secretion (NCE102), transcriptional regulators (FLO11, MHY1, D01353 g, RSFA, E23925g or MAF1), vacuolar proteolysis targets in Y. lipolytica (ATGs, VPSs, HSE1, PRB1, PRC1, PEP4) or growth arrest (CLN1) upon rs-Prots overproduction.