Document Detail

An expanded genetic code with a functional quadruplet codon.
MedLine Citation:
PMID:  15138302     Owner:  NLM     Status:  MEDLINE    
With few exceptions the genetic codes of all known organisms encode the same 20 amino acids, yet all that is required to add a new building block are a unique tRNA/aminoacyl-tRNA synthetase pair, a source of the amino acid, and a unique codon that specifies the amino acid. For example, the amber nonsense codon, TAG, together with orthogonal Methanococcus jannaschii or Escherichia coli tRNA/synthetase pairs have been used to genetically encode a variety of unnatural amino acids in E. coli and yeast, respectively. However, the availability of noncoding triplet codons ultimately limits the number of amino acids encoded by any organism. Here, we report the design and generation of an orthogonal synthetase/tRNA pair derived from archaeal tRNA(Lys) sequences that efficiently and selectively incorporates an unnatural amino acid into proteins in response to the quadruplet codon, AGGA. Frameshift suppression with L-homoglutamine (hGln) does not significantly affect protein yields or cell growth rates and is mutually orthogonal with amber suppression, permitting the simultaneous incorporation of two unnatural amino acids, hGln and O-methyl-L-tyrosine, at distinct positions within myoglobin. This work suggests that neither the number of available triplet codons nor the translational machinery itself represents a significant barrier to further expansion of the genetic code.
J Christopher Anderson; Ning Wu; Stephen W Santoro; Vishva Lakshman; David S King; Peter G Schultz
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2004-05-11
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  101     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2004 May 
Date Detail:
Created Date:  2004-05-19     Completed Date:  2004-07-06     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7566-71     Citation Subset:  IM    
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
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MeSH Terms
Amino Acids / genetics,  metabolism*
Amino Acyl-tRNA Synthetases / genetics,  metabolism*
Evolution, Molecular
Genetic Code*
Lysine-tRNA Ligase / metabolism
Pyrococcus horikoshii / enzymology,  genetics*
RNA, Transfer / metabolism
Reg. No./Substance:
0/Amino Acids; 0/Codon; 9014-25-9/RNA, Transfer; EC 6.1.1.-/Amino Acyl-tRNA Synthetases; EC Ligase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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