ArticleNature communications2024
Understanding activity-stability tradeoffs in biocatalysts by enzyme proximity sequencing.
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.
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Who cites it
28 citing papers in PubMed, 53 citations in OpenAlex.
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- Overestimating zero-shot fitness prediction: Broad benchmarks mask local failures and practical limitations.bioRxiv : the preprint server for biology · 2026Article
- SynFit: Synergistic Contrastive Learning for Multi-Objective Protein Fitness Prediction and Optimization.bioRxiv : the preprint server for biology · 2026Article
- A Needle-Like MOFzyme with High Aspect Ratio and Extended pH/Temperature Working Ranges for Total Antioxidant Capacity Determination and Oxidant-/Light-Free Dye Degradation.ChemistryOpen · 2026Article
- Deep learning-guided dual-fitness evolution of T7 RNA polymerase for enhanced stability and activity.Nucleic acids research · 2026Article
- DEX: a consensus-based amino acid exchangeability measure for improved codon substitution modelling.bioRxiv : the preprint server for biology · 2026Article
- Tryptophanase Mining and Characterization toward the Biological Production of Indole Derivatives.ACS omega · 2026Article
- Dynamic bond-driven encapsulation of enzymes in metal-organic frameworks beyond pore size constraints.Nature communications · 2026Article
- A general protocol for engineering metal-oxo-chain standing frameworks.National science review · 2026Article
- Decoding the substrate specificity landscape of a promiscuous enzyme through multi-substrate mutational scanning.Nature communications · 2026Article
- Enzymatic Glucosylation Enhances the Solubility of Niclosamide but Abrogates Its Therapeutic Efficacy.ACS omega · 2026Article
- Synthesis and Characterization of Rubisco-Magnesium Complexes for Potential Gas Adsorption Applications.ACS omega · 2026Article
- Comparative phylotranscriptomics reveals glycolytic adaptation associated with prolonged larval development in the coastal slipper lobsterAnimal cells and systems · 2026Article
- PTM encoding: decoding the mechanisms of exercise-induced metabolic memory through spatiotemporal modification networks.Frontiers in sports and active living · 2026Review
- Complete genome sequencing ofFrontiers in microbiology · 2026Article
- Best Practices for Machine Learning-Assisted Protein Engineering.Journal of chemical information and modeling · 2025Review
- Approaches for regulating enzyme activities: Recent advances in experiment and computation.Current opinion in structural biology · 2025Review
- Data-efficient protein mutational effect prediction with weak supervision by molecular simulation and protein language models.Briefings in bioinformatics · 2025Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
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.
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Registered trials
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.