Enzymatic Hydrolytic Dehalogenation of Chlorinated Aromatic Compounds

Colorado School Of Mines, Golden CO

Investigators

Abstract

With the support of the Chemistry of Life Processes program in the Division of Chemistry, Professor Holz from the Colorado School of Mines will investigate the enzymatic biodegradation of the fungicide chlorothalonil and the herbicide atrazine, two halogenated aromatic hydrocarbons, which are highly toxic and carcinogenic. Their removal is challenging because they are chemically stable, resistant to degradation, and lipophilic. Nevertheless, some enzymes can catalyze their degradation to less-toxic analogs. The project focuses on understanding the mechanism of enzymatic biodegradation. The project will also provide exceptional training for undergraduate and graduate-level scientists and serve as the basis for community engagement activities. This research project seeks to gain molecular-level insights into two Zn(II)-dependent hydrolytic dehalogenases, namely a chlorothalonil dehalogenase (Chd) and a triazine hydrolase (TrzN). These enzymes degrade chlorothalonil and atrazine, respectively, to their corresponding less-toxic alcohol derivatives. The catalytic mechanisms of both Chd and TrzN will be examined using an interdisciplinary approach that includes kinetics, spectroscopic, biochemical, computational, X-ray methods, and biomaterial synthesis. Three important unanswered questions will be addressed: (i) What is the allosteric and structural influence on Chd activity, including its impact on active site residues that are catalytically important?, (ii) Can biomaterials developed using Chd and TrzN be used to degrade chlorothalonil and atrazine, respectively, at room temperature and physiological pH? and (iii) Can Chd catalytically dehalogenate fluoro- and bromo-substrate analogs of chlorothalonil and inform the discovery of new dehalogenases? This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.