Research in the Drienovská Lab focuses on expanding the catalytic potential of enzymes beyond what is accessible in nature. We combine genetic code expansion, protein engineering, mechanistic enzymology, X-ray crystallography, and computational protein design, including de novo design, to create new-to-nature biocatalysts with tailored reactivity, selectivity, and function.

By incorporating non-canonical amino acids into proteins, we introduce novel chemical functionalities into enzyme active sites, enabling catalytic strategies that are inaccessible to the natural amino acid repertoire. We integrate these approaches with structural biology and computational methods to understand, design, and optimize enzyme structures and catalytic mechanisms. This enables the development of artificial and hybrid catalytic systems, including organocatalytic and photocatalytic enzymes, in which non-natural functionalities are directly integrated into the protein scaffold.

In parallel, we investigate fundamental questions at the interface of chemistry and biology, including how new catalytic functions emerge, how enzyme mechanisms can be reprogrammed, and how protein environments can be engineered to support catalysis under non-natural reaction conditions.