Mechanistic and Synthetic Enzymology

To establish a well-defined structure-function relationship of enzymes and gain a deeper understanding of the mechanisms of enzymatic reactions, we routinely characterize the enzymes under study with a myriad of biochemical, biophysical, and computational tools. Our established structural (X-ray crystallography, cryoEM) and computational (in silico docking, molecular dynamics simulation) biology platforms not only provide deeper insights into enzyme mechanism, but also practical guidance to enzyme design and optimization.

To facilitate the deployment of enzymes into a harsh environment, we are developing protein scaffolds that can be used to immobilize or encapsulate enzymes, lending the enzymes extra support or shield to prolong their lifespan. Such scaffolds can also bring together different enzymes involved in the same reaction cascade, making the overall catalysis more efficient.

As a simple, programmable method, the CRISPR-Cas system holds great promise for genome editing of target organisms with unprecedented speed and precision. The relatively large molecular weight and low thermostability of the Cas enzymes are some of the current roadblocks to the wider application of the system. By combining genome data mining with semi-rational design and directed evolution, we are en route to identifying novel Cas enzymes as well as improving existing ones that are more compact and thermostable. Such characteristics will make the Cas enzymes more industrially applicable.