This award by the Chemistry of Life Processes in the Chemistry Division, is funding Drs. Bennett and Holz from Marquette University to investigate how the enzyme Nitrile hydratase (NHase) transforms chemical groups called nitriles into amides under ambient conditions. Interestingly, NHases can hydrate not only nitriles found in biological systems but also a wide range of synthetic nitriles. Hence NHases are extensively used in preparative organic chemistry laboratories and in the industrial production of acrylamide and nicotinamide. NHases have also proven useful in the cleanup of nitrile-based chemicals and pesticides from the environment and are thus becoming increasingly recognized as a new type of "Green" catalyst. Knowledge of the mechanisms that underscore their chemical reactivity and applications could provide an impetus for the development of new biocatalysts. Drs. Bennett and Holz's research use an interdisciplinary experimental approach to gain insight into how nitriles are hydrated by NHases. Their research and education efforts help promote teaching, training and learning for graduate and undergraduate students, particularly those from underrepresented groups. Their research also enhances the infrastructure for research and education at Marquette University.

While the biological roles of NHases are not well understood, they likely include nutrient metabolism, nitrile detoxification and/or nutrient assimilation. Nitriles are most commonly found in biological systems as cyanoglycosides or cyanolipids, but many plants also produce nitriles such as ricin and beta-cyanoalanine for self-defense purposes. The major impediment to understanding their biological and bioremediation roles is the lack of understanding of their catalytic mechanism. Drs. Bennett and Holz provide molecular level insight into the hydration of nitriles by NHases using a combination of kinetics, spectroscopy, biochemistry, computational chemistry, and X-ray crystallography studies. Answers to three specific questions are sought: (1) What is the transition-state of nitrile hydration? (2) Is a transient disulfide bond between the sulfenic acid cyclic intermediate and the axial alpha-Cys ligand required for catalysis? and (3) What controls metallocenter assembly in Fe-type NHases? Successful completion of this project enhances our understanding of the catalytic mechanism of NHases and stimulate development of engineered bioremediation catalysts.

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.

National Science Foundation (NSF)
Division of Chemistry (CHE)
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Catalina Achim
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Marquette University
United States
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