Evidence map›Paper›PMID 36465553›Full record

ArticleNature catalysis2022

Bypassing evolutionary dead ends and switching the rate-limiting step of a human immunotherapeutic enzyme.

John Blazeck, Christos S Karamitros, Kyle Ford, Catrina Somody, Ahlam Qerqez, Kyle Murray, Nathaniel T Burkholder, Nicholas Marshall, Anirudh Sivakumar, Wei-Cheng Lu and 15 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature catalysis, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.7field-weighted citation impact, top 10% 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

15 citing papers in PubMed, 20 citations in OpenAlex.

  1. Promiscuity-Guided Enzyme Evolution via Substrate Multiplexed Screening.Angewandte Chemie (International ed. in English) · 2026
    Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
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  8. Determining the Serum Stability of Human Adenosine Deaminase 1 Enzyme.Journal of visualized experiments : JoVE · 2024
    Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Targeted Mutation of a Non-catalytic Gating Residue Increases the Rate ofJournal of agricultural and food chemistry · 2023
    Article
  14. Article
  15. Article
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

25 authors at 7 institutions in 3 countries.

John BlazeckDepartment of Chemical Engineering, University of Texas at Austin (UT Austin), Austin, Texas, USA.
Christos S KaramitrosDepartment of Chemical Engineering, University of Texas at Austin (UT Austin), Austin, Texas, USA.
Kyle FordDepartment of Chemical Engineering, University of Texas at Austin (UT Austin), Austin, Texas, USA.
Catrina SomodyDepartment of Chemical Engineering, University of Texas at Austin (UT Austin), Austin, Texas, USA.
Ahlam QerqezDepartment of Chemical Engineering, University of Texas at Austin (UT Austin), Austin, Texas, USA.
Kyle MurrayDepartment of Chemistry and Biochemistry, The University of Texas at Dallas, Richardson, Texas, USA.
Nathaniel T BurkholderDepartment of Molecular Biosciences, University of Texas at Austin (UT Austin), Austin, Texas, USA.
Nicholas MarshallDepartment of Chemical Engineering, University of Texas at Austin (UT Austin), Austin, Texas, USA.
Anirudh SivakumarDepartment of Chemical Engineering, University of Texas at Austin (UT Austin), Austin, Texas, USA.
Wei-Cheng LuDepartment of Chemical Engineering, University of Texas at Austin (UT Austin), Austin, Texas, USA.
Bing TanDepartment of Chemical Engineering, University of Texas at Austin (UT Austin), Austin, Texas, USA.
Candice LambDepartment of Chemical Engineering, University of Texas at Austin (UT Austin), Austin, Texas, USA.
Yuri TannoDepartment of Chemical Engineering, University of Texas at Austin (UT Austin), Austin, Texas, USA.
Menna Y SiddiquiDepartment of Chemical Engineering, University of Texas at Austin (UT Austin), Austin, Texas, USA.
Norah AshouraDepartment of Molecular Biosciences, University of Texas at Austin (UT Austin), Austin, Texas, USA.
Silvia ComaIkena Oncology, Cambridge, Massachusetts, USA.
Xiaoyan M ZhangIkena Oncology, Cambridge, Massachusetts, USA.
Karen McGovernIkena Oncology, Cambridge, Massachusetts, USA.
Yoichi KumadaDepartment of Molecular Chemistry and Engineering, Kyoto Institute of Technology, Kyoto, Japan.
Yan Jessie ZhangDepartment of Molecular Biosciences, University of Texas at Austin (UT Austin), Austin, Texas, USA.
Mark ManfrediIkena Oncology, Cambridge, Massachusetts, USA.
Kenneth A JohnsonDepartment of Molecular Biosciences, University of Texas at Austin (UT Austin), Austin, Texas, USA.
Sheena D'ArcyDepartment of Chemistry and Biochemistry, The University of Texas at Dallas, Richardson, Texas, USA.
Everett StoneDepartment of Molecular Biosciences, University of Texas at Austin (UT Austin), Austin, Texas, USA.
George GeorgiouDepartment of Chemical Engineering, University of Texas at Austin (UT Austin), Austin, Texas, USA.
The University of Texas at Austin · USKura Oncology (United States) · USLivestrong Foundation · USBoston University · USGeorgia Institute of Technology · USKyoto Institute of Technology · JPThe University of Texas at Dallas · US

Funding

The Role of Dynamics in Regulating Multi-Activity Protein Complexes and ChromatinR35GM133751 · NIGMS · UNIVERSITY OF TEXAS DALLAS · PI Sheena D'Arcy · 2019 to 2026
$2.9M
Human-Enzyme Mediated, Systemic Depletion of Cystine for Cancer Treatment.R01CA189623 · NCI · UNIVERSITY OF TEXAS AT AUSTIN · PI DIGIOVANNI, JOHN, GEORGIOU, GEORGE GEORGIOU · 2014 to 2018
$2.9M
Gene-specific transcriptional silencing directed by dephosphorylation of RNAP IIR01GM104896 · NIGMS · UNIVERSITY OF TEXAS AT AUSTIN · PI ZHANG, YAN JESSIE · 2013 to 2022
$2.4M
Interpretation of the phosphorylation code of RNA polymerase II during eukaryotic transcriptionR01GM125882 · NIGMS · UNIVERSITY OF TEXAS AT AUSTIN · PI BRODBELT, JENNIFER S., ZHANG, YAN JESSIE · 2018 to 2021
$1.4M
NCI NIH HHS R01 CA189623NIGMS NIH HHS R01 GM104896NIGMS NIH HHS R01 GM125882NIGMS NIH HHS R35 GM133751
6 · The paper itself

Abstract

The Trp metabolite kynurenine (KYN) accumulates in numerous solid tumours and mediates potent immunosuppression. Bacterial kynureninases (KYNases), which preferentially degrade kynurenine, can relieve immunosuppression in multiple cancer models, but immunogenicity concerns preclude their clinical use, while the human enzyme (HsKYNase) has very low activity for kynurenine and shows no therapeutic effect. Using fitness selections, we evolved a HsKYNase variant with 27-fold higher activity, beyond which exploration of >30 evolutionary trajectories involving the interrogation of >10

Identifiers

PMID36465553
PMCPMC9717613
OpenAlexW4306809720

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.