Evidence map›Paper›PMID 36550233›Full record

ArticleNature chemistry2023

Genetically programmed cell-based synthesis of non-natural peptide and depsipeptide macrocycles.

Martin Spinck, Carlos Piedrafita, Wesley E Robertson, Thomas S Elliott, Daniele Cervettini, Daniel de la Torre, Jason W Chin

Open access · hybridAbstract read
In one paragraph

Article in Nature chemistry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
4.7field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

33 citing papers in PubMed, 59 citations in OpenAlex.

  1. Review
  2. It's a Gas: Bioconjugation With Vapor-Phase Reagents.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026
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  9. Automated orthogonal tRNA generation.Nature chemical biology · 2025
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  11. Review
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  15. Recent advances in the expanding genetic code.Current opinion in chemical biology · 2024
    Review
  16. Review
  17. Review
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Martin Spinck *Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.ORCID 0000-0002-4708-8500
Carlos Piedrafita *Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.ORCID 0000-0002-1788-2033
Wesley E RobertsonMedical Research Council Laboratory of Molecular Biology, Cambridge, UK. wesr@mrc-lmb.cam.ac.uk.ORCID 0000-0001-9812-8288
Thomas S ElliottMedical Research Council Laboratory of Molecular Biology, Cambridge, UK.
Daniele CervettiniMedical Research Council Laboratory of Molecular Biology, Cambridge, UK.ORCID 0000-0002-8159-1222
Daniel de la TorreMedical Research Council Laboratory of Molecular Biology, Cambridge, UK.
Jason W ChinMedical Research Council Laboratory of Molecular Biology, Cambridge, UK. chin@mrc-lmb.cam.ac.uk.ORCID 0000-0003-1219-4757
MRC Laboratory of Molecular Biology · GB

Funding

Medical Research Council MC_U105181009Medical Research Council MC_UP_A024_1008
6 · The paper itself

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.

Indexed as

Amino Acyl-tRNA SynthetasesDepsipeptidesAmino AcidsCodonHydroxy AcidsRNA, TransferAmino AcidsAmino Acyl-tRNA SynthetasesCodonDepsipeptidesHydroxy AcidsRNA, Transfer

Identifiers

PMID36550233
PMCPMC9836938
OpenAlexW4312114429

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.