Diethyl phthalate (DEP) perturbs nitrogen metabolism in Saccharomyces cerevisiae

Phthalates are ubiquitously used as plasticizers in various consumer care products. Diethyl phthalate (DEP), one of the main phthalates, elicits developmental and reproductive toxicities but the underlying mechanisms are not fully understood. Chemogenomic profiling of DEP in S. cerevisiae revealed that two transcription factors Stp1 and Dal81 involved in the Ssy1-Ptr5-Ssy5 (SPS) amino acid-sensing pathway provide resistance to DEP. Growth inhibition of yeast cells by DEP was stronger in poor nitrogen medium in comparison to nitrogen-rich medium. Addition of amino acids to nitrogen-poor medium suppressed DEP toxicity. Catabolism of amino acids via the Ehrlich pathway is required for suppressing DEP toxicity. Targeted metabolite analyses showed that DEP treatment alters the amino acid profile of yeast cells. We propose that DEP inhibits the growth of yeast cells by affecting nitrogen metabolism and discuss the implications of our findings on DEP-mediated toxic effects in humans.

Automated summary

Phthalates are commonly used as plasticizers in consumer care products. One specific phthalate, diethyl phthalate (DEP), has been found to have developmental and reproductive toxicities. The mechanisms underlying these toxic effects are not fully understood, but a chemogenomic profiling study in yeast identified two transcription factors that provide resistance to DEP. DEP's inhibitory effect on yeast growth was stronger in nitrogen-poor conditions, and the addition of amino acids suppressed its toxicity. Targeted metabolite analyses revealed that DEP treatment alters the amino acid profile of yeast cells, suggesting that DEP affects nitrogen metabolism. These findings have implications for understanding the toxic effects of DEP in humans.