Escherichia coliwith a 57-codon genetic code

Abstract The near-universal genetic code of living organisms uses 64 codons to encode the 20 canonical amino acids in protein synthesis. Here we design and generate a variant of Escherichia coli with a 4 Mb synthetic genome in which we replace every known occurrence of six sense codons and a stop codon with synonymous codons. We thereby recode 10 5 codons to create an organism with a 57-codon genetic code; this organism – which we name Syn57 – uses 55 codons to encode the 20 canonical amino acids.