Design, synthesis, and testing toward a 57-codon genome

Author:

Ostrov Nili1,Landon Matthieu123,Guell Marc14,Kuznetsov Gleb15,Teramoto Jun16,Cervantes Natalie1,Zhou Minerva7,Singh Kerry7,Napolitano Michael G.18,Moosburner Mark1,Shrock Ellen1,Pruitt Benjamin W.4,Conway Nicholas4,Goodman Daniel B.14,Gardner Cameron L.1,Tyree Gary1,Gonzales Alexandra1,Wanner Barry L.19,Norville Julie E.1,Lajoie Marc J.1,Church George M.14

Affiliation:

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

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

3. Ecole des Mines de Paris, Mines Paristech, Paris 75272, France.

4. Wyss Institute for Biologically Inspired Engineering, Boston, MA 02115, USA.

5. Program in Biophysics, Harvard University, Boston, MA 02115, USA.

6. Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA.

7. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

8. Program in Biological and Biomedical Sciences, Harvard University, Cambridge, MA 02138, USA.

9. Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.

Abstract

Recoding and repurposing genetic codons By recoding bacterial genomes, it is possible to create organisms that can potentially synthesize products not commonly found in nature. By systematic replacement of seven codons with synonymous alternatives for all protein-coding genes, Ostrov et al. recoded the Escherichia coli genome. The number of codons in the E. coli genetic code was reduced from 64 to 57 by removing instances of the UAG stop codon and excising two arginine codons, two leucine codons, and two serine codons. Over 90% functionality was successfully retained. In 10 cases, reconstructed bacteria were not viable, but these few failures offered interesting insights into genome-design challenges and what is needed for a viable genome. Science , this issue p. 819

Funder

U.S Department of Energy

Defense Advanced Research Projects Agency

NSF

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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