Chemical-genetic interaction landscape of mono-(2-ethylhexyl)-phthalate using chemogenomic profiling in yeast

Integration of chemical-genetic interaction data with biological functions provides a mechanistic understanding of how toxic compounds affect cells. Mono-(2-ethylhexyl)-phthalate (MEHP) is an active metabolite of di-2-ethylhexyl phthalate (DEHP), a commonly used plasticizer. MEHP adversely affects human health causing hepatotoxicity and reproductive toxicity. How MEHP affects cellular physiology is not fully understood. We utilized a genome-wide competitive fitness-based assay called ‘chemogenomic profiling’ to determine the genetic interaction map of MEHP in Saccharomyces cerevisiae. We demonstrate the MEHP affects several biological functions including amino acid uptake, vesicular trafficking, ionic homeostasis, cell membrane and cell wall integrity. Our work provides a basis for further investigation of MEHP toxicity in humans.