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Total synthesis of Escherichia coli with a recoded genome
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Journal Article
Total synthesis of Escherichia coli with a recoded genome
2019
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/44
/ 42
/ 42/70
/ 45
/ 45/70
/ 631/61
/ 64
/ Bacteria
/ Codon, Terminator - genetics
/ Codons
/ Design
/ DNA
/ E coli
/ Escherichia coli - growth & development
/ Escherichia coli - metabolism
/ Genetically modified organisms
/ Genome, Bacterial - genetics
/ Genomes
/ Genomics
/ Humanities and Social Sciences
/ Proteins
/ RNA
/ Science
