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PMID: 24136966 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Genomically recoded organisms expand biological functions.

Science (New York, N.Y.) ·Vol. 342 ·No. 6156 ·2013-10-18 ·Pages 357-60

Lajoie MJ, Rovner AJ, Goodman DB, Aerni HR, Haimovich AD, Kuznetsov G, Mercer JA, Wang HH, Carr PA, Mosberg JA, Rohland N, Schultz PG, Jacobson JM, Rinehart J, Church GM, Isaacs FJ

Abstract

We describe the construction and characterization of a genomically recoded organism (GRO). We replaced all known UAG stop codons in Escherichia coli MG1655 with synonymous UAA codons, which permitted the deletion of release factor 1 and reassignment of UAG translation function. This GRO exhibited improved properties for incorporation of nonstandard amino acids that expand the chemical diversity of proteins in vivo. The GRO also exhibited increased resistance to T7 bacteriophage, demonstrating that new genetic codes could enable increased viral resistance.

MeSH Terms
Amino Acid Substitution/genetics Amino Acids/genetics Bacteriophage T7/physiology Codon, Terminator/genetics Escherichia coli/genetics,virology Escherichia coli Proteins/genetics Genetic Engineering Genome, Bacterial Organisms, Genetically Modified/genetics,virology Peptide Chain Termination, Translational/genetics Peptide Termination Factors/genetics
Chemicals
Amino Acids Codon, Terminator Escherichia coli Proteins Peptide Termination Factors
Authors & Affiliations
16 authors, click to expand affiliations / ORCID
Lajoie Marc J
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Rovner Alexis J
Goodman Daniel B
Aerni Hans-Rudolf
Haimovich Adrian D
Kuznetsov Gleb
Mercer Jaron A
Wang Harris H
Carr Peter A
Mosberg Joshua A
Rohland Nadin
Schultz Peter G
Jacobson Joseph M
Rinehart Jesse
Church George M
Isaacs Farren J
References (25)
25 references, click to expand
  1. Synthetic constructs in/for the environment: managing the interplay between natural and engineered Biology.
    FEBS Lett. 2012 Jul 16;586(15):2199-206 PMID: 22710182
  2. Codon reassignment in the Escherichia coli genetic code.
    Nucleic Acids Res. 2010 Dec;38(22):8188-95 PMID: 20702426
  3. An expanded genetic code with a functional quadruplet codon.
    Proc Natl Acad Sci U S A. 2004 May 18;101(20):7566-71 PMID: 15138302
  4. Efficient decoding of the UAG triplet as a full-fledged sense codon enhances the growth of a prfA-deficient strain of Escherichia coli.
    J Bacteriol. 2012 May;194(10):2606-13 PMID: 22427623
  5. Encoding multiple unnatural amino acids via evolution of a quadruplet-decoding ribosome.
    Nature. 2010 Mar 18;464(7287):441-4 PMID: 20154731
  6. Enhanced multiplex genome engineering through co-operative oligonucleotide co-selection.
    Nucleic Acids Res. 2012 Sep 1;40(17):e132 PMID: 22638574
  7. Programming cells by multiplex genome engineering and accelerated evolution.
    Nature. 2009 Aug 13;460(7257):894-898 PMID: 19633652
  8. Creation of a bacterial cell controlled by a chemically synthesized genome.
    Science. 2010 Jul 2;329(5987):52-6 PMID: 20488990
  9. Engineered bacteriophage-defence systems in bioprocessing.
    Nat Rev Microbiol. 2006 May;4(5):395-404 PMID: 16715051
  10. An enhanced system for unnatural amino acid mutagenesis in E. coli.
    J Mol Biol. 2010 Jan 15;395(2):361-74 PMID: 19852970
  11. Precise manipulation of chromosomes in vivo enables genome-wide codon replacement.
    Science. 2011 Jul 15;333(6040):348-53 PMID: 21764749
  12. RF1 knockout allows ribosomal incorporation of unnatural amino acids at multiple sites.
    Nat Chem Biol. 2011 Sep 18;7(11):779-86 PMID: 21926996
  13. Evolutionary robustness of an optimal phenotype: re-evolution of lysis in a bacteriophage deleted for its lysin gene.
    J Mol Evol. 2005 Aug;61(2):181-91 PMID: 16096681
  14. Red queen dynamics of protein translation.
    J Theor Biol. 2002 Sep 7;218(1):97-109 PMID: 12297073
  15. Transfer ribonucleic acid-mediated suppression of termination codons in Escherichia coli.
    Microbiol Rev. 1988 Sep;52(3):354-74 PMID: 3054467
  16. Ribosome-mediated incorporation of a non-standard amino acid into a peptide through expansion of the genetic code.
    Nature. 1992 Apr 9;356(6369):537-9 PMID: 1560827
  17. Expanding the genetic code of Escherichia coli with phosphoserine.
    Science. 2011 Aug 26;333(6046):1151-4 PMID: 21868676
  18. Noncanonical amino acids in the interrogation of cellular protein synthesis.
    Acc Chem Res. 2011 Sep 20;44(9):677-85 PMID: 21815659
  19. Probing the limits of genetic recoding in essential genes.
    Science. 2013 Oct 18;342(6156):361-3 PMID: 24136967
  20. Expression in Escherichia coli of chemically synthesized genes for human insulin.
    Proc Natl Acad Sci U S A. 1979 Jan;76(1):106-10 PMID: 85300
  21. Collective evolution and the genetic code.
    Proc Natl Acad Sci U S A. 2006 Jul 11;103(28):10696-701 PMID: 16818880
  22. The establishment of genetically engineered canola populations in the U.S.
    PLoS One. 2011;6(10):e25736 PMID: 21998689
  23. Enhanced phosphoserine insertion during Escherichia coli protein synthesis via partial UAG codon reassignment and release factor 1 deletion.
    FEBS Lett. 2012 Oct 19;586(20):3716-22 PMID: 22982858
  24. Near-cognate suppression of amber, opal and quadruplet codons competes with aminoacyl-tRNAPyl for genetic code expansion.
    FEBS Lett. 2012 Nov 2;586(21):3931-7 PMID: 23036644
  25. Adding new chemistries to the genetic code.
    Annu Rev Biochem. 2010;79:413-44 PMID: 20307192
Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
DOI
10.1126/science.1241459
Published
2013-10-18
Pages
357-60
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC4924538
Subset
IM
Grants
NIGMS NIH HHS · T32GM07205 · United States
NIDDK NIH HHS · K01DK089006 · United States
NIH HHS · DP5 OD009172 · United States
NIEHS NIH HHS · 27306C0002 · United States
NIDDK NIH HHS · K01 DK089006 · United States
NIGMS NIH HHS · T32 GM007205 · United States
NIH HHS · 1DP5OD009172-01 · United States
NIEHS NIH HHS · 27304C0002 · United States
External Links
PubMed source DOI: 10.1126/science.1241459 PMC Full Text View journal details
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