Evidence map›Paper›PMID 31777933›Full record

ArticleNucleic acids research2020

Evolution-guided engineering of small-molecule biosensors.

Tim Snoek, Evan K Chaberski, Francesca Ambri, Stefan Kol, Sara P Bjørn, Bo Pang, Jesus F Barajas, Ditte H Welner, Michael K Jensen, Jay D Keasling

Abstract read
In one paragraph

Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.

0numbers the graph read from it
0cells of the map it votes in
57citing 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

57 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Mining Genetically Encoded Biosensors from Filamentous Fungi.Journal of fungi (Basel, Switzerland) · 2026
    Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Metabolic Engineering ofMolecules (Basel, Switzerland) · 2024
    Review
  20. Review
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

10 authors.

Tim SnoekNovo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kgs. Lyngby, Denmark.
Evan K ChaberskiNovo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kgs. Lyngby, Denmark.
Francesca AmbriNovo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kgs. Lyngby, Denmark.
Stefan KolNovo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kgs. Lyngby, Denmark.
Sara P BjørnNovo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kgs. Lyngby, Denmark.
Bo PangJoint BioEnergy Institute, Emeryville, CA, USA.
Jesus F BarajasJoint BioEnergy Institute, Emeryville, CA, USA.
Ditte H WelnerNovo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kgs. Lyngby, Denmark.
Michael K JensenNovo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kgs. Lyngby, Denmark.
Jay D KeaslingNovo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kgs. Lyngby, Denmark.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Allosteric transcription factors (aTFs) have proven widely applicable for biotechnology and synthetic biology as ligand-specific biosensors enabling real-time monitoring, selection and regulation of cellular metabolism. However, both the biosensor specificity and the correlation between ligand concentration and biosensor output signal, also known as the transfer function, often needs to be optimized before meeting application needs. Here, we present a versatile and high-throughput method to evolve prokaryotic aTF specificity and transfer functions in a eukaryote chassis, namely baker's yeast Saccharomyces cerevisiae. From a single round of mutagenesis of the effector-binding domain (EBD) coupled with various toggled selection regimes, we robustly select aTF variants of the cis,cis-muconic acid-inducible transcription factor BenM evolved for change in ligand specificity, increased dynamic output range, shifts in operational range, and a complete inversion-of-function from activation to repression. Importantly, by targeting only the EBD, the evolved biosensors display DNA-binding affinities similar to BenM, and are functional when ported back into a prokaryotic chassis. The developed platform technology thus leverages aTF evolvability for the development of new host-agnostic biosensors with user-defined small-molecule specificities and transfer functions.

Indexed as

Biosensing TechniquesDirected Molecular EvolutionDNADNA-Binding ProteinsEscherichia coliGene LibraryGenes, ReporterGenetic EngineeringGreen Fluorescent ProteinsLigandsModels, MolecularMutagenesisProtein DomainsProtein Structure, SecondarySaccharomyces cerevisiaeSorbic AcidDNADNA-Binding ProteinsGreen Fluorescent ProteinsLigandsmuconic acidSorbic AcidTranscription Factors

Identifiers

PMID31777933
PMCPMC6943132

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.