Brian G. Fox

Photo of Brian Fox
Marvin J. Johnson Professor in Fermentation Biochemistry
Chair, Department of Biochemistry
B.A., Carleton College
Ph.D., University of Minnesota
Phone: (608) 262-9708
Email: bgfox@biochem.wisc.edu

Biochemical, catalytic, and spectroscopic studies of redox active enzymes; protein engineering

Crystal structure of CelE from Ruminoclostridium thermocellum
Crystal structure of CelE from
Ruminoclostridium thermocellum,
a CMX enzyme structure studied
and solved in the Fox Lab. 

My lab specializes in the study of enzymes and their functions. Much of our current work is funded through the Great Lakes Bioenergy Research Center (GLBRC). Our goal is to use synthetic biology techniques to discover new enzymes that can break down recalcitrant polysaccharides, like the cellulose in wood, for use as biofuel feedstock.

Broadly stated, our research goals are to define the structure and reactivity of carbohydrate active enzymes, to probe the catalytic contributions of the active site protein residues, and to determine the consequences of protein-protein and protein-substrate interactions on the outcomes of enzymatic catalysis. From years of work on projects in our Center for Eukaryotic Structural Genomics (part of the NIH Protein Structure Initiative), we have a wealth of structural data from the genomes of various organisms but lack information on gene function. Using our cell-free protein synthesis platforms, we are able to quickly functionally characterize enzymes and ultimately crystallize them to document their structure. We then further this important basic research by narrowing down the enzymes that have useful applications for producing biofuels or advancing processes like bioremediation.

A phylogenetic tree of the clade known as GH5_4
A phylogenetic tree of the clade
known as GH5_4, which grad
students in the Fox Lab exhaust-
ively tested for multifunctional
enzymes using cell-free protein
synthesis.

Part of this project includes enzymes that have multiple functions. They are called CMX enzymes for the three different substrates they can act upon: cellulose, mannan, and xylan. When generating bioenergy, enzyme cocktails are used to break down products like corn waste or switchgrass into simple sugars. By finding enzymes that can act in more than one way, the enzymes cocktails can become more efficient and less expensive. We are interested in understanding the specificity and stability of CMX enzymes and engineering new ones with enhanced catalytic properties. Students in my lab have had opportunities to collaborate with biotechnology companies and apply their work to helping solve real problems in industry.

My lab is also involved in the study of a human stearoyl-CoA desaturase in order to understand its mechanism and role in lipid biosynthesis, as well as the study of Streptomyces bacteria to find beneficial enzymes and metabolites they can generate. We regularly have high school students and undergraduates learning biotechnology techniques in our lab. Our highly collaborative efforts involve studies from basic research to translatable biotechnology, drawing on aspects of chemical biology, analytical chemistry, genetic engineering, and classical biochemistry.

I am also the director of the Biotechnology Training Program at UW-Madison, a pre-doctoral training program funded by the NIH to provide opportunities for graduate students to engage in cross-disciplinary study and industrial biotechnology research.