Biocatalysis and Synthetic Biology
Biocatalysis has emerged as a promising method to address challenges in synthetic chemistry and synthetic biology to achieve high reactivity and selectivity. To expand the synthetic scope of biocatalysis, we aim to develop novel artificial biocatalysts that access new chemistry by protein engineering. Our strategies involve rational design, bioinformatic search, computational modeling and directed evolution. We start with computational modeling to mimic the structural features of the native enzymes within small and robust protein scaffolds. Once new reactivities are discovered, we further apply directed evolution to enhance the yield and selectivity. In the past studies, we have achieved higher enzyme stability, greater production yield, deeper understanding of the enzyme mechanisms and new-to-nature reactivities. For example, we have demonstrated that incorporating unnatural amino acids (UAAs) and synthetic cofactors into small and compact protein scaffolds could lead to diversified reactivities. We are also designing biocatalysts to convert biomass to value-added products, for example, lignin degradation, polysaccharide degradation and polyketide generation.