BS Lafayette College, 2007
PhD Yale University, 2012
My training is in bioinorganic chemistry, with a particular focus on understanding hydrolysis prone metals, like titanium and vanadium, in biological environments.
The aqueous chemistry of hydrolysis-prone metals is often avoided due to their reactivity with water. Avoiding hydrolysis through careful ligand choice opens new uses for these metals. Two such metals, titanium and vanadium, have many uses as catalysts and materials under non-natural conditions. Harnessing their reactivity with water using biological ligands will lead to novel applications of these metals. While titanium and vanadium are not commonly native to enzymes, their reactivity with water can be controlled in the binding sites of many natural proteins. We design novel enzyme active sites to bind hydrolysis-prone metals and utilize their reactivity to generate new enzymatic activities.
Many de novo designed proteins bind metals, however none have been reported to bind hydrolysis-prone metals, such as titanium and vanadium. These metals are relatively abundant, but underused in catalysis compared to precious metals. We have recently shown the ability of our enzymes to stabilize and functionalize titanium, providing the first report of a titanium enzyme, as well as the ability of our model system to mimic natural binuclear zinc hydrolases. Both our titanium and zinc enzymes are able to cleave DNA, showing their potential to act as therapeutics. We are now working to understand structure function relationships of these enzymes, and their ability to function against a variety of substrates.
Projects in the Buettner lab include: the design and development of new active sites in our current protein scaffolds to optimize metal binding as well as enzymatic activity; characterization of metal binding using a suite of biophysical techniques; and the optimization of enzymatic activity studies.