| Autor: |
Martin Spinck, Carlos Piedrafita, Wesley E. Robertson, Thomas S. Elliott, Daniele Cervettini, Daniel de la Torre, Jason W. Chin |
| Přispěvatelé: |
Spinck, Martin [0000-0002-4708-8500], Piedrafita, Carlos [0000-0002-1788-2033], Robertson, Wesley E [0000-0001-9812-8288], Cervettini, Daniele [0000-0002-8159-1222], Chin, Jason W [0000-0003-1219-4757], Apollo - University of Cambridge Repository |
| Rok vydání: |
2023 |
| Předmět: |
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| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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