Senior Investigators: Prof. John Hartwig (UI-UC), Prof. Huimin Zhao (UI-UC).

Directed evolution has become a proven method for the development of enzymes that display non-natural functions. Most directed evolution experiments have been conducted on enzymes such as lipases and nitrile hydrolases that lack transition metal-containing active sites. However, a few studies have been reported on the development of heme-iron systems, including one that operates by a peroxide shunt pathway without cofactors, and these studies demonstrate that directed evolution can be conducted on metalloenzymes. By combining the expertise of the Hartwig group in the identification and development of transformations useful for synthetic organic chemistry with the expertise of the Zhao group in developing and enacting methods for directed enzyme evolution, we are: 1) developing selective oxidations for reactions useful in organic synthesis; 2) developing selective halogenations that provide building blocks for medicinal chemistry; and 3) developing metalloenzymes that catalyze new classes of enzyme-catalyzed reactions. The capability of metalloenzymes to catalyze amination reactions is limited, but nitrogen-containing molecules serve as a cornerstone of medicinal chemistry. Thus, a portion of our studies on new reactivity will attack the ambitious goal of developing metalloenzymes that catalyze oxidative amination chemistry.

Published Papers:

Nair, N. U.; Zhao, H. “Evolution in Reverse: Engineering a D-Xylose-specific Xylose Reductase” ChemBioChem, 2008, 9, 1213-1215.
(DOI: 10.1002/cbic.200700765)