Abstract: My group develops catalysts that merge the benefits of enzymes and abiotic chemistry. In one research area, we are using DNA as a nano-scaffold to accelerate reactions through pre-organization of multiple abiotic catalysts, akin to enzyme active sites but not limited to the natural amino acids and cofactors. I will describe our development of a platform to rapidly evaluate millions of DNA nanocatalysts using DNA barcoding and combinatorial synthesis, thus mimicking the process of directed evolution in discovering highly active abiotic catalyst systems. In our second research area, we are developing ultrahigh-throughput chemogenetic directed evolution platforms to enhance the activity of natural enzymes in abiotic contexts. I will describe our development of yeast display platforms to discover enzyme mutants with improved activity for diverse applications, including recycling of synthetic plastics and proteomic mapping in living cells.