Abstract 1377 Using cryo-EM structures of Escherchia coli ribosomes to expand the substrate scope of translation

Engineering the Escherichia coli ribosome to accept non-α-amino acid substrates (such as β-amino acids, aminobenzoic acids and α- or β-hydroxy acids) can allow for the recombinant synthesis of sequence defined, non-protein or hybrid polymers. Such molecules can be engineered for specific purposes, such as the creation of protease-resistant peptidomimetics, macrocyclic drug candidates, and foldamers. Although it has been demonstrated that the wild-type E. coli ribosome can accept a range of non-α-amino acid monomers as substrates and incorporate them into proteins or peptides, the efficiency of incorporation remains low and are constrained to in vitro experiments.