ArticleNature communications2017
Single-mutation fitness landscapes for an enzyme on multiple substrates reveal specificity is globally encoded.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
What it found
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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.
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Who cites it
75 citing papers in PubMed, 164 citations in OpenAlex.
- Evolutionary strategies of late-stage diversification in bacterial biosynthetic gene clusters.Essays in biochemistry · 2026Review
- Using enantioselective biosensors to evolve asymmetric biocatalysts.Nature chemical biology · 2026Article
- Promiscuity-Guided Enzyme Evolution via Substrate Multiplexed Screening.Angewandte Chemie (International ed. in English) · 2026Review
- How far can you go? Extrapolating values of catalytic activity from known protein landscapes in natural and directed evolution.Chemical Society reviews · 2026Review
- Multidomain DNA-Protein Mining Reveals Polymorphic Variations in RhlB Enhancing Monorhamnolipid Biosynthesis.ACS synthetic biology · 2026Article
- DEX: a consensus-based amino acid exchangeability measure for improved codon substitution modelling.bioRxiv : the preprint server for biology · 2026Article
- Intrinsic dataset features drive mutational effect prediction by protein language models.bioRxiv : the preprint server for biology · 2026Article
- Decoding the substrate specificity landscape of a promiscuous enzyme through multi-substrate mutational scanning.Nature communications · 2026Article
- A Three-Module Machine Learning Framework for Protein Sequence- and Temperature-DependentACS synthetic biology · 2025Article
- Approaches for regulating enzyme activities: Recent advances in experiment and computation.Current opinion in structural biology · 2025Review
- The role of plasmid copy number and mutation rate in evolutionary outcomes.Nature ecology & evolution · 2025Article
- Exploring antibiotic resistance in diverse homologs of the dihydrofolate reductase protein family through broad mutational scanning.Science advances · 2025Article
- Clonal interference and genomic repair during strain coexistence in the gut.PLoS genetics · 2025Article
- Ultrahigh-Throughput Activity Engineering of Promiscuous Amidases through a Fluorescence-Activated Cell Sorting Assay.ACS catalysis · 2025Article
- Combining Oligo Pools and Golden Gate Cloning to Create Protein Variant Libraries or Guide RNA Libraries for CRISPR Applications.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Microbial amidases: Characterization, advances and biotechnological applications.Biotechnology notes (Amsterdam, Netherlands) · 2025Review
- Article
- Frustration can Limit the Adaptation of Promiscuous Enzymes Through Gene Duplication and Specialisation.Journal of molecular evolution · 2024Article
- Opportunities and Challenges for Machine Learning-Assisted Enzyme Engineering.ACS central science · 2024Review
- Understanding activity-stability tradeoffs in biocatalysts by enzyme proximity sequencing.Nature communications · 2024Article
15 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Our lack of total understanding of the intricacies of how enzymes behave has constrained our ability to robustly engineer substrate specificity. Furthermore, the mechanisms of natural evolution leading to improved or novel substrate specificities are not wholly defined. Here we generate near-comprehensive single-mutation fitness landscapes comprising >96.3% of all possible single nonsynonymous mutations for hydrolysis activity of an amidase expressed in E. coli with three different substrates. For all three selections, we find that the distribution of beneficial mutations can be described as exponential, supporting a current hypothesis for adaptive molecular evolution. Beneficial mutations in one selection have essentially no correlation with fitness for other selections and are dispersed throughout the protein sequence and structure. Our results further demonstrate the dependence of local fitness landscapes on substrate identity and provide an example of globally distributed sequence-specificity determinants for an enzyme.
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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.