| Autor: |
Fredens J; Medical Research Council Laboratory of Molecular Biology, Cambridge, UK., Wang K; Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA., de la Torre D; Medical Research Council Laboratory of Molecular Biology, Cambridge, UK., Funke LFH; Medical Research Council Laboratory of Molecular Biology, Cambridge, UK., Robertson WE; Medical Research Council Laboratory of Molecular Biology, Cambridge, UK., Christova Y; Medical Research Council Laboratory of Molecular Biology, Cambridge, UK., Chia T; Medical Research Council Laboratory of Molecular Biology, Cambridge, UK., Schmied WH; Medical Research Council Laboratory of Molecular Biology, Cambridge, UK., Dunkelmann DL; Medical Research Council Laboratory of Molecular Biology, Cambridge, UK., Beránek V; Medical Research Council Laboratory of Molecular Biology, Cambridge, UK., Uttamapinant C; Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.; School of Biomolecular Science and Engineering, Vidyasirimedhi Institute of Science and Technology (VISTEC), Rayong, Thailand., Llamazares AG; Medical Research Council Laboratory of Molecular Biology, Cambridge, UK., Elliott TS; Medical Research Council Laboratory of Molecular Biology, Cambridge, UK., Chin JW; Medical Research Council Laboratory of Molecular Biology, Cambridge, UK. chin@mrc-lmb.cam.ac.uk. |
| Abstrakt: |
Nature uses 64 codons to encode the synthesis of proteins from the genome, and chooses 1 sense codon-out of up to 6 synonyms-to encode each amino acid. Synonymous codon choice has diverse and important roles, and many synonymous substitutions are detrimental. Here we demonstrate that the number of codons used to encode the canonical amino acids can be reduced, through the genome-wide substitution of target codons by defined synonyms. We create a variant of Escherichia coli with a four-megabase synthetic genome through a high-fidelity convergent total synthesis. Our synthetic genome implements a defined recoding and refactoring scheme-with simple corrections at just seven positions-to replace every known occurrence of two sense codons and a stop codon in the genome. Thus, we recode 18,214 codons to create an organism with a 61-codon genome; this organism uses 59 codons to encode the 20 amino acids, and enables the deletion of a previously essential transfer RNA. |
Full text from SpringerLink