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Science 20 April 2001:
Vol. 292. no. 5516, pp. 498 - 500
DOI: 10.1126/science.1060077

Reports

Expanding the Genetic Code of Escherichia coli

Lei Wang,1 Ansgar Brock,2 Brad Herberich,1 Peter G. Schultz12*

A unique transfer RNA (tRNA)/aminoacyl-tRNA synthetase pair has been generated that expands the number of genetically encoded amino acids in Escherichia coli. When introduced into E. coli, this pair leads to the in vivo incorporation of the synthetic amino acid O-methyl-L-tyrosine into protein in response to an amber nonsense codon. The fidelity of translation is greater than 99%, as determined by analysis of dihydrofolate reductase containing the unnatural amino acid. This approach should provide a general method for increasing the genetic repertoire of living cells to include a variety of amino acids with novel structural, chemical, and physical properties not found in the common 20 amino acids.

1 Department of Chemistry and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
2 Genomics Institute of the Novartis Research Foundation, 3115 Merryfield Row, San Diego, CA 92121, USA.
*   To whom correspondence should be addressed. E-mail: schultz{at}scripps.edu


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