Evidence map›Paper›PMID 37264106›Full record

ArticleNature chemistry2023

Expanding the substrate scope of pyrrolysyl-transfer RNA synthetase enzymes to include non-α-amino acids in vitro and in vivo.

Riley Fricke, Cameron V Swenson, Leah Tang Roe, Noah Xue Hamlish, Bhavana Shah, Zhongqi Zhang, Elise Ficaretta, Omer Ad, Sarah Smaga, Christine L Gee and 2 more

Abstract read
PubMed Full text at PMC Publisher
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 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
–field-weighted citation impact
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

27 citing papers in PubMed.

  1. Review
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  3. Co-Translational Incorporation of (Journal of the American Chemical Society · 2026
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  9. Review
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  13. Peptide Backbone Editing via Post-Translational O to C Acyl Shift.Journal of the American Chemical Society · 2025
    Article
  14. Review
  15. Review
  16. Review
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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

12 authors.

Riley Fricke *Department of Chemistry, University of California, Berkeley, CA, USA.ORCID http://orcid.org/0000-0001-9463-6314
Cameron V Swenson *Department of Chemistry, University of California, Berkeley, CA, USA.ORCID http://orcid.org/0000-0002-9896-3539
Leah Tang RoeDepartment of Chemistry, University of California, Berkeley, CA, USA.ORCID http://orcid.org/0000-0002-2487-5587
Noah Xue HamlishCenter for Genetically Encoded Materials, University of California, Berkeley, CA, USA.ORCID http://orcid.org/0000-0003-4318-8675
Bhavana ShahProcess Development, Amgen, Thousand Oaks, CA, USA.
Zhongqi ZhangProcess Development, Amgen, Thousand Oaks, CA, USA.ORCID http://orcid.org/0000-0002-8326-6714
Elise FicarettaCenter for Genetically Encoded Materials, University of California, Berkeley, CA, USA.
Omer AdDepartment of Chemistry, Yale University, New Haven, CT, USA.
Sarah SmagaDepartment of Chemistry, University of California, Berkeley, CA, USA.ORCID http://orcid.org/0000-0003-3469-2642
Christine L GeeDepartment of Molecular and Cell Biology, University of California, Berkeley, CA, USA.ORCID http://orcid.org/0000-0002-2632-6418
Abhishek ChatterjeeCenter for Genetically Encoded Materials, University of California, Berkeley, CA, USA.ORCID http://orcid.org/0000-0002-6231-5302
Alanna SchepartzDepartment of Chemistry, University of California, Berkeley, CA, USA. schepartz@berkeley.edu.ORCID http://orcid.org/0000-0003-2127-3932

Funding

User Training and OutreachP30GM124169 · NIGMS · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI Gregory L Hura · 2017 to 2026
$28.6M
Eliminating Critical Systematic Errors In Structural Biology With Next-Generation SimulationR01GM124149 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HOLTON, JAMES M · 2017 to 2024
$2.5M
Howard Hughes Medical InstituteNIGMS NIH HHS P30 GM124169NIGMS NIH HHS R01 GM124149
6 · The paper itself

Abstract

The absence of orthogonal aminoacyl-transfer RNA (tRNA) synthetases that accept non-L-α-amino acids is a primary bottleneck hindering the in vivo translation of sequence-defined hetero-oligomers and biomaterials. Here we report that pyrrolysyl-tRNA synthetase (PylRS) and certain PylRS variants accept α-hydroxy, α-thio and N-formyl-L-α-amino acids, as well as α-carboxy acid monomers that are precursors to polyketide natural products. These monomers are accommodated and accepted by the translation apparatus in vitro; those with reactive nucleophiles are incorporated into proteins in vivo. High-resolution structural analysis of the complex formed between one PylRS enzyme and a m-substituted 2-benzylmalonic acid derivative revealed an active site that discriminates prochiral carboxylates and accommodates the large size and distinct electrostatics of an α-carboxy substituent. This work emphasizes the potential of PylRS-derived enzymes for acylating tRNA with monomers whose α-substituent diverges substantially from the α-amine of proteinogenic amino acids. These enzymes or derivatives thereof could synergize with natural or evolved ribosomes and/or translation factors to generate diverse sequence-defined non-protein heteropolymers.

Indexed as

Amino Acyl-tRNA SynthetasesAmino AcidsLysineRNA, TransferAmino AcidsAmino Acyl-tRNA SynthetasesLysineRNA, Transfer

Identifiers

PMID37264106
PMCPMC10322718

What Socratic 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 Socratic graph.