Molecular Evolution Directs Protein Translation Using Unnatural Amino Acids

Abstract Unnatural amino acids have in recent years established their importance in a wide range of fields, from pharmaceuticals to polymer science. Unnatural amino acids can increase the number of chemical groups within proteins and thus expand or enhance biological function. Our ability to utilize these important building blocks, however, has been limited by the inherent difficulty in incorporating these molecules into proteins. To address this challenge, researchers have examined how the canonical twenty amino acids are incorporated, regulated, and modified in nature. This review focuses on achievements and techniques used to engineer the ribosomal protein‐translation machinery, including the introduction of orthogonal translation components, how directed evolution enhances the incorporation of unnatural amino acids, and the potential utility of ancient biomolecules for this process. © 2015 by John Wiley & Sons, Inc.