Diethyl phthalate (DEP) perturbs nitrogen metabolism in Saccharomyces cerevisiae

Abstract

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.

Reversing the directionality of reactions between non-oxidative pentose phosphate pathway and glycolytic pathway boosts mycosporine-like amino acid production in Saccharomyces cerevisiae

“…Overnight cultures were grown in synthetic complete media, quenched by addition to twice the volume of methanol (preincubated at -80 °C) and immediately pelleted at 4000 g in a pre-cooled centrifuge (4 °C) for 2 min. Supernatants were discarded and pellets were processed as previously described [25,26].…”

Reversing the directionality of reactions between non-oxidative pentose phosphate pathway and glycolytic pathway boosts mycosporine-like amino acid production in Saccharomyces cerevisiae

“…Overnight cultures were grown in synthetic complete media, quenched by addition to twice the volume of methanol (preincubated at -80°C) and immediately pelleted at 4500 rpm in a pre-cooled centrifuge (4°C) for 2 min. Supernatants were discarded and pellets were processed as previously described ( [24], [25]). 13 Carbon-labelling Yeast strains were grown in synthetic complete media with 2% unlabelled glucose until they reached logphase.…”