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Total synthesis of Escherichia coli with a recoded genome

Author

Listed:
  • Julius Fredens

    (Medical Research Council Laboratory of Molecular Biology)

  • Kaihang Wang

    (Medical Research Council Laboratory of Molecular Biology
    California Institute of Technology)

  • Daniel Torre

    (Medical Research Council Laboratory of Molecular Biology)

  • Louise F. H. Funke

    (Medical Research Council Laboratory of Molecular Biology)

  • Wesley E. Robertson

    (Medical Research Council Laboratory of Molecular Biology)

  • Yonka Christova

    (Medical Research Council Laboratory of Molecular Biology)

  • Tiongsun Chia

    (Medical Research Council Laboratory of Molecular Biology)

  • Wolfgang H. Schmied

    (Medical Research Council Laboratory of Molecular Biology)

  • Daniel L. Dunkelmann

    (Medical Research Council Laboratory of Molecular Biology)

  • Václav Beránek

    (Medical Research Council Laboratory of Molecular Biology)

  • Chayasith Uttamapinant

    (Medical Research Council Laboratory of Molecular Biology
    Vidyasirimedhi Institute of Science and Technology (VISTEC))

  • Andres Gonzalez Llamazares

    (Medical Research Council Laboratory of Molecular Biology)

  • Thomas S. Elliott

    (Medical Research Council Laboratory of Molecular Biology)

  • Jason W. Chin

    (Medical Research Council Laboratory of Molecular Biology)

Abstract

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.

Suggested Citation

  • Julius Fredens & Kaihang Wang & Daniel Torre & Louise F. H. Funke & Wesley E. Robertson & Yonka Christova & Tiongsun Chia & Wolfgang H. Schmied & Daniel L. Dunkelmann & Václav Beránek & Chayasith Utta, 2019. "Total synthesis of Escherichia coli with a recoded genome," Nature, Nature, vol. 569(7757), pages 514-518, May.
  • Handle: RePEc:nat:nature:v:569:y:2019:i:7757:d:10.1038_s41586-019-1192-5
    DOI: 10.1038/s41586-019-1192-5
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    Citations

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    Cited by:

    1. Yuting Chen & Eriona Hysolli & Anlu Chen & Stephen Casper & Songlei Liu & Kevin Yang & Chenli Liu & George Church, 2022. "Multiplex base editing to convert TAG into TAA codons in the human genome," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    2. Donghui Choe & Connor A. Olson & Richard Szubin & Hannah Yang & Jaemin Sung & Adam M. Feist & Bernhard O. Palsson, 2024. "Advancing the scale of synthetic biology via cross-species transfer of cellular functions enabled by iModulon engraftment," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    3. Shuangying Jiang & Zhouqing Luo & Jie Wu & Kang Yu & Shijun Zhao & Zelin Cai & Wenfei Yu & Hui Wang & Li Cheng & Zhenzhen Liang & Hui Gao & Marco Monti & Daniel Schindler & Linsen Huang & Cheng Zeng &, 2023. "Building a eukaryotic chromosome arm by de novo design and synthesis," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    4. Alessandro L. V. Coradini & Christopher Ne Ville & Zachary A. Krieger & Joshua Roemer & Cara Hull & Shawn Yang & Daniel T. Lusk & Ian M. Ehrenreich, 2023. "Building synthetic chromosomes from natural DNA," Nature Communications, Nature, vol. 14(1), pages 1-12, December.

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