112.4 - Structure-Based Strategies for Rieske Oxygenase Catalysis

Jennifer Bridwell-Rabb (University of Michigan), Jianxin Liu (University of Michigan), Jiayi Tian (University of Michigan), Zerick Dill (University of Michigan)

Rieske Oxygenases are enzymes that showcase the remarkable ability to functionalize an inert C–H bond. These enzymes use a Rieske [2Fe-2S] cluster and a mononuclear iron center to bind and activate molecular oxygen. Using these metallocenters, Rieske Oxygenases have been shown to catalyze a variety of reactions, including one, two, and sequential hydroxylation reactions. This chemistry is important to the biosynthetic pathways of multiple organisms and is thus attractive for industrially building and tailoring natural product scaffolds. Similarly, the chemistry of the Rieske Oxygenases is abundant in degradative pathways and therefore offers compelling strategies for degrading environmental pollutants. However, a traditional lack of structure–function information for this expansive class of enzymes has restricted our ability to capitalize on these important and diverse catalytic strategies. Therefore, our laboratory is working to understand the architectural features of these enzymes that allow them to control and facilitate catalysis. Here, we present our current understanding of how these enzymes selectively catalyze reactions and use structure to guide chemical outcome.