Non‐Canonical Amino Acids in Protein Polymer Design

Protein polymers can be prepared with essentially absolute control of chain length, sequence, and stereochemistry through biological synthesis in microbial hosts. But for the polymer chemist, the twenty “canonical” amino acids provide an unacceptably small set of starting materials for macromolecular design. In the past several years, powerful techniques have been developed to introduce non‐natural (non‐canonical) amino acids containing a wide variety of functional groups into recombinant proteins. This review presents the methods currently available for the introduction of non‐natural amino acids into engineered proteins both in vitro and in vivo. Methods for multiple‐ and single‐site introduction are described. Recent applications of these methods are also addressed, particularly the development of biosensors, novel surfaces, and materials.