Enzymes are the most powerful catalysts on earth, capable of accelerating the rates of reactions by up to 1017-fold. However, the enzymes we observe in nature have evolved for specific reactions - they are not as efficient (in general) when it comes to “new” reactions that might be essential for the catalysis of new biosynthetic reactions to make molecules that are important in industry or medicine. Natural enzymes are also limited by the 20 naturally occurring amino acids and the suite of available natural cofactors. In this project, we will design novel enzymes, using structural and computation tools, that can utilize novel synthetic cofactors and unnatural amino acids. These will be used to make chemical building blocks for the pharmaceutical industry in a “green” process and to convert agricultural waste, such as lignin, into high value commodities for industry. This project will involve collaboration with partners within the Centre of Excellence in Peptide and Protein Science.