The exposure to a growing number of environmental contaminants has been associated with the increasing incidence of metabolic disorders and cancers in organisms. While over 350,000 compounds have been registered worldwide for production and use, the toxicity testing of each individual compound by traditional methods is infeasible, due to the high time requirements and financial costs. Herein, we propose a protein-guided ‘top-down’ strategy for identifying toxic contaminants from environmental mixtures—which consist of millions of unknown compounds—at the exposome-wide level. Three case studies from our group will be presented to demonstrate the strengths of this novel protein-guided strategy: In the first study, recombinant human nuclear receptors were used to directly isolate their high affinity ligands from extracts of indoor dust, resulting in a new indoor transformation product of bisphenol A, being identified as a high affinity ligand binding to estrogen related receptor gamma. In the second study, the protein-guided approach was applied to isolate predominant antibacterial reagents from natural products and sewage sludge. In the third study, to further identify electrophiles that exert toxicities by covalently modifying proteins, the top-down strategy will be employed to identify the toxicity drivers in treated drinking water consisting of hundreds of disinfection by-products.
Hui Peng is an assistant professor at the Chemistry Department at the University of Toronto. Hui obtained his BSc from Peking University (PKU) in 2008 and then stayed at PKU for his Ph.D. research (2013). After graduating, Hui spent three years as a postdoctoral fellow at the University of Toronto and University of Saskatchewan. Hui joined the Department of Chemistry at the University of Toronto as a faculty member in 2017, where he currently leads his environmental chemical biology team. His current research is focused on the building of the first protein-contaminant interaction network.