Genomically Recoded Organisms Expand Biological Functions

Author:

Lajoie Marc J.12,Rovner Alexis J.34,Goodman Daniel B.15,Aerni Hans-Rudolf46,Haimovich Adrian D.34,Kuznetsov Gleb1,Mercer Jaron A.7,Wang Harris H.8,Carr Peter A.9,Mosberg Joshua A.12,Rohland Nadin1,Schultz Peter G.10,Jacobson Joseph M.1112,Rinehart Jesse46,Church George M.113,Isaacs Farren J.34

Affiliation:

1. Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.

2. Program in Chemical Biology, Harvard University, Cambridge, MA 02138, USA.

3. Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USA.

4. Systems Biology Institute, Yale University, West Haven, CT 06516, USA.

5. Program in Medical Engineering and Medical Physics, Harvard–Massachusetts Institute of Technology (MIT) Division of Health Sciences and Technology, Cambridge, MA 02139, USA.

6. Department of Cellular and Molecular Physiology, Yale University, New Haven, CT 06520, USA.

7. Harvard College, Cambridge, MA 02138, USA.

8. Department of Systems Biology, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.

9. MIT Lincoln Laboratory, Lexington, MA 02420, USA.

10. Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA.

11. Center for Bits and Atoms, MIT, Cambridge, MA 02139, USA.

12. MIT Media Lab, MIT, Cambridge, MA 02139, USA.

13. Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.

Abstract

Changing the Code Easily and efficiently expanding the genetic code could provide tools to genome engineers with broad applications in medicine, energy, agriculture, and environmental safety. Lajoie et al. (p. 357 ) replaced all known UAG stop codons with synonymous UAA stop codons in Escherichia coli MG1655, as well as release factor 1 (RF1; terminates translation at UAG), thereby eliminating natural UAG translation function without impairing fitness. This made it possible to reassign UAG as a dedicated codon to genetically encode nonstandard amino acids while avoiding deleterious incorporation at native UAG positions. The engineered E. coli incorporated nonstandard amino acids into its proteins and showed enhanced resistance to bacteriophage T7. In a second paper, Lajoie et al. (p. 361 ) demonstrated the recoding of 13 codons in 42 highly expressed essential genes in E. coli. Codon usage was malleable, but synonymous codons occasionally were nonequivalent in unpredictable ways.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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