Engineering Biocatalysts for a Sustainable Future

Our research in enzyme engineering focuses on the structure-guided and rational modification of enzymes to improve stability, catalytic efficiency, and robustness for biomedical and biotechnological applications. We have engineered coenzyme B12-dependent glycerol dehydratase by reinforcing the α–β subunit interface, achieving up to 24-fold enhanced resistance to inactivation while maintaining catalytic performance and significantly reducing coenzyme B12 requirements. In parallel, we have engineered α-ketoglutaric semialdehyde dehydrogenase (KGSADH) through substrate- and cofactor-binding pocket optimization, resulting in variants with lower Km values, higher catalytic efficiency, and improved tolerance to toxic intermediates, enabling increased 3-hydroxypropionic acid production in microbial systems.

In addition, we apply computational modeling and structure-based mutagenesis to engineer enzymes beyond metabolic pathways. This includes the rational optimization of prokaryotic Argonaute nucleases, where targeted mutations significantly enhanced DNA cleavage activity at physiological temperatures, expanding their potential for programmable nucleic-acid applications. We also contribute mechanistic and structural insights into coenzyme B12-dependent enzymes, integrating biochemical, computational, and engineering approaches to guide the development of more robust and efficient biocatalysts for translational research and industrial biotechnology .