Often, naturally occurring enzymes are slow or inefficient catalysts when asked to perform new transformations. We use protein engineering to improve enzyme function and develop new functions. This engineering is often done sequentially over multiple rounds, resulting in highly improved catalysts, through a process called directed evolution.
Our scientists investigate enzymes and enzyme function using a variety of biophysical, spectroscopical, and kinetic techniques. We alter the reactivity of natural cofactors to unveil new mechanistic insights. Some of our current work involves elucidating the structural determinates of pyridoxal-5’-phospate (PLP, vitamin B6) chemistry, and then leveraging these findings to develop new-to-nature reactions.
We aim to develop reactions that make useful chemical bonds. Our lab focuses on engineering C-C and C-X bond forming enzymes and assembling useful building blocks for downstream chemoenzymatic synthesis of natural products. In addition to engineering enzymes with high turnover number and broad specificity, we develop transformations and enzymatic cascades that rely upon easily accessible starting materials, straightforward reaction set up, and immediately useful chemical products. We rely on both enzymatic synthesis and traditional organic chemistry to accomplish our synthetic goals.
Bioinformatic and Computational Tools
To efficiently navigate sequence space, we implement bioinformatic and computational tools to profile sequence-activity relationships. We develop linear regression models to predict which residues should be targeted via mutagenesis to aid our protein engineering campaigns. Additionally, we use sequence similarity network analysis to visualize the diversity across protein families.
Our lab is actively developing methods to improve upon directed evolution methodology. Projects in the lab also focus on developing enzymes that catalyze new-to-nature chemistry via incorporation of new-to-nature cofactors and active site residues. Through metabolic engineering and non-canonical amino acid incorporation strategies, we hope to streamline the development and procurement of powerful novel biocatalysts.