Expanding the Scope of Protein Biosynthesis by Altering the Methionyl-tRNA Synthetase Activity of a Bacterial Expression Host

The incorporation of amino acids into proteins in vivo is controlled by the aminoacyl-tRNA synthetases. The successful incorporation of a nonnatural amino acid, trans-crotylglycine (Tcg), into a protein has now been achieved by increasing the methionyl-tRNA synthetase activity of a bacterial expression host (see scheme). The incorporation of Tcg into proteins creates new opportunities for macromolecular synthesis through genetic engineering, due to the rich chemistry of the olefinic side chain.