Evidence map›Paper›PMID 38418512›Full record

ArticleNature communications2024

Understanding activity-stability tradeoffs in biocatalysts by enzyme proximity sequencing.

Rosario Vanella, Christoph Küng, Alexandre A Schoepfer, Vanni Doffini, Jin Ren, Michael A Nash

Open access · goldAbstract 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 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
15.0field-weighted citation impact, top 1% 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

28 citing papers in PubMed, 53 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Complete genome sequencing ofFrontiers in microbiology · 2026
    Article
  18. Best Practices for Machine Learning-Assisted Protein Engineering.Journal of chemical information and modeling · 2025
    Review
  19. Review
  20. 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

6 authors at 1 institution in 1 country.

Rosario VanellaInstitute of Physical Chemistry, Department of Chemistry, University of Basel, 4058, Basel, Switzerland. rosario.vanella@unibas.ch.ORCID 0000-0001-7503-1627
Christoph KüngInstitute of Physical Chemistry, Department of Chemistry, University of Basel, 4058, Basel, Switzerland.ORCID 0000-0002-3164-6213
Alexandre A SchoepferInstitute of Physical Chemistry, Department of Chemistry, University of Basel, 4058, Basel, Switzerland.ORCID 0000-0001-8051-0091
Vanni DoffiniInstitute of Physical Chemistry, Department of Chemistry, University of Basel, 4058, Basel, Switzerland.ORCID 0009-0005-1457-6371
Jin RenInstitute of Physical Chemistry, Department of Chemistry, University of Basel, 4058, Basel, Switzerland.ORCID 0000-0001-8143-0472
Michael A NashInstitute of Physical Chemistry, Department of Chemistry, University of Basel, 4058, Basel, Switzerland. michael.nash@unibas.ch.ORCID 0000-0003-3842-1567
University of Basel · CH

Funding

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation) 200021_191962
6 · The paper itself

Abstract

Understanding the complex relationships between enzyme sequence, folding stability and catalytic activity is crucial for applications in industry and biomedicine. However, current enzyme assay technologies are limited by an inability to simultaneously resolve both stability and activity phenotypes and to couple these to gene sequences at large scale. Here we present the development of enzyme proximity sequencing, a deep mutational scanning method that leverages peroxidase-mediated radical labeling with single cell fidelity to dissect the effects of thousands of mutations on stability and catalytic activity of oxidoreductase enzymes in a single experiment. We use enzyme proximity sequencing to analyze how 6399 missense mutations influence folding stability and catalytic activity in a D-amino acid oxidase from Rhodotorula gracilis. The resulting datasets demonstrate activity-based constraints that limit folding stability during natural evolution, and identify hotspots distant from the active site as candidates for mutations that improve catalytic activity without sacrificing stability. Enzyme proximity sequencing can be extended to other enzyme classes and provides valuable insights into biophysical principles governing enzyme structure and function.

Indexed as

Mutation, MissenseEnzyme StabilityMutation

Identifiers

PMID38418512
PMCPMC10902396
OpenAlexW4392239232

What OpenQuestion 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 OpenQuestion graph.