LAUSR

Significance The ability of nucleic acids to catalyze reactions is important in the context of the origin of life and biomedical applications. However, the catalytic power of standard nucleic acids assembled from just four nucleotide building blocks is limited when compared with that of proteins. Using an artificially expanded genetic information system (AEGIS) carrying extra synthetic nucleotides, we show that DNA libraries with increased chemical diversity, higher information density, and larger searchable sequence spaces are at least one order of magnitude richer reservoirs of molecules able to catalyze the cleavage of RNA than DNA libraries built from a standard four-nucleotide alphabet. The AEGISzyme described here represents the first time that catalysts have been evolved from libraries built from expanded genetic alphabets.