Evidence map›Paper›PMID 32284585›Full record

ArticleNature biotechnology2020

Rapid discovery and evolution of orthogonal aminoacyl-tRNA synthetase-tRNA pairs.

Daniele Cervettini, Shan Tang, Stephen D Fried, Julian C W Willis, Louise F H Funke, Lucy J Colwell, Jason W Chin

Open access · greenAbstract read
In one paragraph

Article in Nature biotechnology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed
5.4field-weighted citation impact, top 3% 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

73 citing papers in PubMed, 117 citations in OpenAlex.

  1. Review
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  3. Article
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  5. Article
  6. Co-Translational Incorporation of (Journal of the American Chemical Society · 2026
    Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Automated orthogonal tRNA generation.Nature chemical biology · 2025
    Article
  15. Article
  16. Article
  17. Substrate recognition by a peptide-aminoacyl-tRNA ligase.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  18. Review
  19. BeyondChemical reviews · 2025
    Review
  20. Review

13 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 2 countries.

Daniele CervettiniMedical Research Council Laboratory of Molecular Biology, Cambridge, UK.ORCID http://orcid.org/0000-0002-8159-1222
Shan TangMedical Research Council Laboratory of Molecular Biology, Cambridge, UK.ORCID http://orcid.org/0000-0003-4483-1108
Stephen D FriedMedical Research Council Laboratory of Molecular Biology, Cambridge, UK.ORCID http://orcid.org/0000-0003-2494-2193
Julian C W WillisMedical Research Council Laboratory of Molecular Biology, Cambridge, UK.ORCID http://orcid.org/0000-0002-2655-2183
Louise F H FunkeMedical Research Council Laboratory of Molecular Biology, Cambridge, UK.ORCID http://orcid.org/0000-0003-1219-9005
Lucy J ColwellDepartment of Chemistry, Cambridge University, Cambridge, UK.ORCID http://orcid.org/0000-0003-3148-0337
Jason W ChinMedical Research Council Laboratory of Molecular Biology, Cambridge, UK. chin@mrc-lmb.cam.ac.uk.ORCID http://orcid.org/0000-0003-1219-4757
MRC Laboratory of Molecular Biology · GBBroad Institute · USJohns Hopkins University · USUniversity of Cambridge · GB

Funding

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

Abstract

A central challenge in expanding the genetic code of cells to incorporate noncanonical amino acids into proteins is the scalable discovery of aminoacyl-tRNA synthetase (aaRS)-tRNA pairs that are orthogonal in their aminoacylation specificity. Here we computationally identify candidate orthogonal tRNAs from millions of sequences and develop a rapid, scalable approach-named tRNA Extension (tREX)-to determine the in vivo aminoacylation status of tRNAs. Using tREX, we test 243 candidate tRNAs in Escherichia coli and identify 71 orthogonal tRNAs, covering 16 isoacceptor classes, and 23 functional orthogonal tRNA-cognate aaRS pairs. We discover five orthogonal pairs, including three highly active amber suppressors, and evolve new amino acid substrate specificities for two pairs. Finally, we use tREX to characterize a matrix of 64 orthogonal synthetase-orthogonal tRNA specificities. This work expands the number of orthogonal pairs available for genetic code expansion and provides a pipeline for the discovery of additional orthogonal pairs and a foundation for encoding the cellular synthesis of noncanonical biopolymers.

Indexed as

Amino Acid SequenceAmino Acyl-tRNA SynthetasesComputer SimulationEscherichia coliGene Expression Regulation, BacterialGreen Fluorescent ProteinsProtein BindingRNA, TransferSubstrate SpecificityAmino Acyl-tRNA SynthetasesGreen Fluorescent ProteinsRNA, Transfer

Identifiers

PMID32284585
PMCPMC7116527
OpenAlexW3015450180

What OpenQuestion holds

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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.