Evidence map›Paper›PMID 39562775›Full record

ArticleNature communications2024

Highly multiplexed design of an allosteric transcription factor to sense new ligands.

Kyle K Nishikawa, Jackie Chen, Justin F Acheson, Svetlana V Harbaugh, Phil Huss, Max Frenkel, Naia Novy, Hailey R Sieren, Ella C Lodewyk, Daniel H Lee and 3 more

Abstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing 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

17 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. Review
  8. Article
  9. Programming Next-Generation Synthetic Biosensors by Genetic Circuit Design.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  10. Article
  11. Article
  12. Review
  13. Unusually broad-spectrum small-molecule sensing using a single protein scaffold.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  14. Article
  15. Article
  16. Review
  17. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Kyle K Nishikawa *Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA.
Jackie Chen *Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA.
Justin F AchesonDepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA.ORCID http://orcid.org/0000-0001-5051-9984
Svetlana V Harbaugh711th Human Performance Wing, Air Force Research Laboratory, Wright Patterson Air Force Base, OH, USA.
Phil HussDepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA.
Max FrenkelDepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA.
Naia NovyDepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA.
Hailey R SierenDepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA.
Ella C LodewykDepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA.
Daniel H LeeDepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA.
Jorge L Chávez711th Human Performance Wing, Air Force Research Laboratory, Wright Patterson Air Force Base, OH, USA.
Brian G FoxDepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA.
Srivatsan RamanDepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA. sraman4@wisc.edu.ORCID http://orcid.org/0000-0003-2461-1589

Funding

GRADUATE TRAINING IN MOLECULAR BIOSCIENCEST32GM007215 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI HULL, CHRISTINA M · 1985 to 2018
$22.5M
Biotechnology Training ProgramT32GM135066 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI SCOTT M. COYLE, BRIAN G FOX · 2020 to 2026
$7.0M
NIGMS NIH HHS T32 GM007215NIGMS NIH HHS T32 GM135066United States Department of Defense | United States Army | U.S. Army Research, Development and Engineering Command | Army Research Office (ARO) W911NF1710043United States Department of Defense | United States Army | U.S. Army Research, Development and Engineering Command | Army Research Office (ARO) W911NF20C0005
6 · The paper itself

Abstract

Allosteric transcription factors (aTF) regulate gene expression through conformational changes induced by small molecule binding. Although widely used as biosensors, aTFs have proven challenging to design for detecting new molecules because mutation of ligand-binding residues often disrupts allostery. Here, we develop Sensor-seq, a high-throughput platform to design and identify aTF biosensors that bind to non-native ligands. We screen a library of 17,737 variants of the aTF TtgR, a regulator of a multidrug exporter, against six non-native ligands of diverse chemical structures - four derivatives of the cancer therapeutic tamoxifen, the antimalarial drug quinine, and the opiate analog naltrexone - as well as two native flavonoid ligands, naringenin and phloretin. Sensor-seq identifies biosensors for each of these ligands with high dynamic range and diverse specificity profiles. The structure of a naltrexone-bound design shows shape-complementary methionine-aromatic interactions driving ligand specificity. To demonstrate practical utility, we develop cell-free detection systems for naltrexone and quinine. Sensor-seq enables rapid and scalable design of new biosensors, overcoming constraints of natural biosensors.

Indexed as

Biosensing TechniquesQuinineAllosteric RegulationFlavanonesHumansLigandsNaltrexoneProtein BindingTamoxifenTranscription FactorsFlavanonesLigandsNaltrexonenaringeninQuinineTamoxifenTranscription Factors

Identifiers

PMID39562775
PMCPMC11577015

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.