• DOI:10.1038/s41586-019-1192-5
• Corpus ID: 205571025

Total synthesis of Escherichia coli with a recoded genome

@article{Fredens2019TotalSO,
  title={Total synthesis of Escherichia coli with a recoded genome},
  author={Julius Fredens and Kaihang Wang and Daniel de la Torre and Louise F. H. Funke and Wesley E. Robertson and Yonka Christova and Tiongsun Chia and Wolfgang Hellmut Schmied and Daniel L. Dunkelmann and V{\'a}clav Ber{\'a}nek and Chayasith Uttamapinant and Andres Gonzalez Llamazares and Thomas S. Elliott and Jason W. Chin},
  journal={Nature},
  year={2019},
  volume={569},
  pages={514-518}
}

• Julius Fredens, Kaihang Wang, +11 authors J. Chin
• Published 1 May 2019
• Biology
• Nature

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.High-fidelity convergent total synthesis is used to produce Escherichia coli with a 61-codon synthetic genome that uses 59 codons to encode all of the canonical amino acids.