Expanding and reprogramming the genetic code

Nature uses a limited, conservative set of amino acids to synthesize proteins. The ability to genetically encode an expanded set of building blocks with new chemical and physical properties is transforming the study, manipulation and evolution of proteins, and is enabling diverse applications, including approaches to probe, image and control protein function, and to precisely engineer therapeutics. Underpinning this transformation are strategies to engineer and rewire translation. Emerging strategies aim to reprogram the genetic code so that noncanonical biopolymers can be synthesized and evolved, and to test the limits of our ability to engineer the translational machinery and systematically recode genomes. A review of the recent developments in reprogramming the genetic code of cells and organisms to include non-canonical amino acids in precisely engineered proteins. Rewriting genetic guidelines In living organisms, proteins that are encoded by DNA are composed of 20 canonical amino acids, with some organisms using up to two additional derivatives. Theoretically, other molecules that are related to these amino acids could form a similar protein backbone and might confer new properties on the proteins. Jason Chin reviews the most recent studies on reprogramming the genetic code, where progress is being made in incorporating these non-canonical (that is, not naturally occurring) amino acids into proteins, even using the cell's own machinery to do so, and without disrupting overall protein function.