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- W4312114429 abstract "Abstract The direct genetically encoded cell-based synthesis of non-natural peptide and depsipeptide macrocycles is an outstanding challenge. Here we programme the encoded synthesis of 25 diverse non-natural macrocyclic peptides, each containing two non-canonical amino acids, in Syn61Δ3-derived cells; these cells contain a synthetic Escherichia coli genome in which the annotated occurrences of two sense codons and a stop codon, and the cognate transfer RNAs (tRNAs) and release factor that normally decode these codons, have been removed. We further demonstrate that pyrrolysyl-tRNA synthetase/tRNA pairs from distinct classes can be engineered to direct the co-translational incorporation of diverse alpha hydroxy acids, with both aliphatic and aromatic side chains. We define 49 engineered mutually orthogonal pairs that recognize distinct non-canonical amino acids or alpha hydroxy acids and decode distinct codons. Finally, we combine our advances to programme Syn61Δ3-derived cells for the encoded synthesis of 12 diverse non-natural depsipeptide macrocycles, which contain two non-canonical side chains and either one or two ester bonds." @default.
- W4312114429 created "2023-01-04" @default.
- W4312114429 creator A5003365197 @default.
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- W4312114429 date "2022-12-22" @default.
- W4312114429 modified "2023-10-06" @default.
- W4312114429 title "Genetically programmed cell-based synthesis of non-natural peptide and depsipeptide macrocycles" @default.
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- W4312114429 doi "https://doi.org/10.1038/s41557-022-01082-0" @default.
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- W4312114429 hasPublicationYear "2022" @default.
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