The classic genetic code encodes 20 naturally occurring amino acids, but there has been considerable effort in designing methods to generate and utilize synthetic amino acids. Mutagenesis is generally restricted to utilizing the genetic code, although various strategies have allowed the incorporation of synthetic amino acids into proteins. The incorporation of synthetic amino acids into proteins is desirable in many instances, for example, having metal-binding or photoreactive properties or enhancing proteins for the design of novel therapeutics. However, limited amounts of protein can be generated by these methods, and thus the rational design of proteins has generally been restricted to the standard genetic code. In the August 15
Chin et al. designed a functional orthogonal pair of a tRNA and aminoacyl-tRNA synthetase that incorporated an unnatural amino acid, while not cross-reacting with any endogenous amino acids. They used the
"This methodology not only removes the constraints imposed by the genetic code on our ability to manipulate protein structure and function in yeast, it provides a gateway to the systematic expansion of the genetic codes of multicellular eukaryotes," conclude the authors.