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 Science, Jason W. Chin and colleagues at the Scripps Research Institute have overcome these limitations through the design of a method to add synthetic amino acid to the genetic code of Saccharomyces cerevisiae (Science, 301:964-967, August 15, 2003).

Chin...

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