Total synthesis of Escherichia coli with a recoded genome

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 Uttamapinant, Andres Gonzalez Llamazares, Thomas S. Elliott and Jason W. Chin ()
Additional contact information
Julius Fredens: Medical Research Council Laboratory of Molecular Biology
Kaihang Wang: Medical Research Council Laboratory of Molecular Biology
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
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

Nature, 2019, vol. 569, issue 7757, 514-518

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41586-019-1192-5

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