Professor Richard Holz

 

Richard C. Holz, Ph.D.
Professor, Dean-Helen Way Klingler College of Arts & Sciences
Phone: (414) 288-7230
E-mail: richard.holz@marquette.edu

Biography

Professor Holz earned his bachelor’s degree at Bemidji State University, his master’s degree at the University of Minnesota-Duluth and his doctorate in chemistry from The Pennsylvania State University.  He was a National Institutes of Health Postdoctoral Research Fellow at the University of Minnesota after which he joined the faculty at Utah State University. He moved to Loyola University Chicago as the Chair of the Chemistry and Biochemistry Department before joining the faculty at Marquette.  He has contributed to more than 100 research articles and co-invented three patents.

Research Interests

The Holz research group interfaces the general areas of bioinorganic chemistry, mechanistic enzymology, and biophysical chemistry. The Holz group is interested in structure/function studies of metalloenzymes some of which are important industrial catalysts or antimicrobial targets. Within these studies, the Holz group uses a wide variety of biochemical and biophysical methods such as enzyme kinetics, site-directed mutagenesis, isothermal titration calorimetry, UV-Vis, NMR and EPR spectroscopies.  Current projects in the Holz group center on an NSF sponsored project to study the catalytic mechanism of nitrile hydratases (NHases) as well as a second project that is examining the catalytic mechanism of the zinc dependent enzymes: i) the dapE-encoded desuccinylase from Haemophilus influenzae (DapE) and ii) the Chlorothalonil hydrolytic dehalogenase from pseudomonas sp. CTN-3 (Chd).

NHases are metalloenzymes in the nitrile degradation pathway that catalyze the hydration of nitriles to their corresponding amides at ambient pressures and temperatures at physiological pH.  NHases have attracted substantial interest as biocatalysts in preparative organic chemistry and are used in many applications such as the large-scale production of acrylamide and nicotinamide.  Because of their exquisite reaction specificity, the nitrile-hydrolyzing potential of NHase enzymes is becoming increasingly recognized as a truly new type of “Green” chemistry.  However, little is understood about how NHase enzymes function.  Therefore, a better understanding of the structure and reaction mechanism of NHase enzymes will enable access to nitrile-hydrolyzing materials with broader substrate ranges, higher activities, and greater stabilities. 

DapE is a member of the lysine biosynthetic pathway, which also produces meso-diaminopimelic acid (meso-DAP), an essential component of bacterial cell wall synthesis.  Disruption of the biosynthesis of meso-DAP has been shown to result in cell death for several bacteria.  Since drug resistance in pathogenic bacteria has increased tremendously in the past few years, DapE’s are potential novel pharmaceutical targets for which a human counterpart does not exist.  Therefore, the design and synthesis of small molecules that inhibit DapE may lead to a new class of antibiotics. 

Chd substitutes a halogen with an hydroxide derived from water on the widely used organochlorine fungicide, Chlorothalonil (5 M kgs used per year in United States alone).  Chlorothalonil is highly toxic so its topical use in agriculture results in the contamination of water, soil, and sediment resulting in pervasive environmental problems.  As only a few enzymes capable of hydrolytically dehalogenating aromatic compounds have been reported, little to nothing is known about how Chd functions.  Therefore, a better understanding of the catalytic mechanism of Chd will provide a platform for the design and synthesis of reagents to clean-up Chlorothalonil environmental contamination.

Recent Publications:

Current Funding:

National Science Foundation (CHE-1808711) 8/15/2018 to 8/14/2021, “Collaborative Research on the Catalytic Mechanism of Nitrile Hydration Catalysts.” The goals of this research are to elucidate the catalytic mechanism of nitrile hydratases (NHases, EC 4.2.1.84) and delineate the steps of metallocenter assembly in Fe-type NHases. 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 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. Knowledge of the mechanisms that underscore their chemical reactivity and applications could provide an impetus for the development of new biocatalysts. The research and education effort help promote teaching, training and learning for graduate and undergraduate students, particularly those from underrepresented groups and also enhances the infrastructure for research and education at Marquette.   

 


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