ReviewProtein science : a publication of the Protein Society2020
A mechanistic view of enzyme evolution.
Review in Protein science : a publication of the Protein Society, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed.
- Application and Molecular Modification of Enzyme in Textile Degumming.Applied biochemistry and biotechnology · 2026Review
- Enhancing Enzyme Activity With Mutation Combinations Guided by Few-Shot Learning and Causal Inference.Angewandte Chemie (International ed. in English) · 2026Article
- Integrative crystallography and molecular dynamics reveal isoform-specific ligand interaction networks in C4 and nonC4 plant NADP-malic enzyme.The Plant journal : for cell and molecular biology · 2026Article
- Engineering ω-transaminase for efficient dihydroxyacetone transamination in serinol biosynthesis starting from methanol.Synthetic and systems biotechnology · 2026Article
- Multidomain DNA-Protein Mining Reveals Polymorphic Variations in RhlB Enhancing Monorhamnolipid Biosynthesis.ACS synthetic biology · 2026Article
- Decoding the substrate specificity landscape of a promiscuous enzyme through multi-substrate mutational scanning.Nature communications · 2026Article
- The bacterial phosphotransferase system-mediated rifampicin phosphorylation: ancestral links to rifampicin-inactivating enzyme.Frontiers in microbiology · 2026Article
- Unlocking Enzyme Discovery: Leveraging Multi-Omics, Machine Learning, and De Novo Design.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Directed evolution of a TNA polymerase identifies independent paths to fidelity and catalysis.Nature communications · 2025Article
- Article
- Protein design drives synthetic biology research of plant natural products.Biodesign research · 2025Review
- Distal mutations enhance catalysis in designed enzymes by facilitating substrate binding and product release.Nature communications · 2025Article
- Multiple transitions to high l-DOPA 4,5-dioxygenase activity reveal molecular pathways to convergent betalain pigmentation in Caryophyllales.The New phytologist · 2025Article
- How enzyme functions evolve: genetic, structural, and kinetic perspectives.Biophysical reviews · 2025Review
- Directed Evolution of a Modular Polyketide Synthase Thioesterase for Generation of a Hybrid Macrocyclic Ring System.ACS catalysis · 2025Article
- Mutations Selectively Evolving Peroxidase Activity Among Alternative Catalytic Functions of Human Glutathione Transferase P1-1.Antioxidants (Basel, Switzerland) · 2024Article
- Article
- Potential involvement of beta-lactamase homologous proteins in resistance to beta-lactam antibiotics in gram-negative bacteria of the ESKAPEE group.BMC genomics · 2024Article
- Unlocking the potential of stimuli-responsive biomaterials for bone regeneration.Frontiers in pharmacology · 2024Review
- Pervasive epistasis exposes intramolecular networks in adaptive enzyme evolution.Nature communications · 2023Article
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
New enzyme functions often evolve through the recruitment and optimization of latent promiscuous activities. How do mutations alter the molecular architecture of enzymes to enhance their activities? Can we infer general mechanisms that are common to most enzymes, or does each enzyme require a unique optimization process? The ability to predict the location and type of mutations necessary to enhance an enzyme's activity is critical to protein engineering and rational design. In this review, via the detailed examination of recent studies that have shed new light on the molecular changes underlying the optimization of enzyme function, we provide a mechanistic perspective of enzyme evolution. We first present a global survey of the prevalence of activity-enhancing mutations and their distribution within protein structures. We then delve into the molecular solutions that mediate functional optimization, specifically highlighting several common mechanisms that have been observed across multiple examples. As distinct protein sequences encounter different evolutionary bottlenecks, different mechanisms are likely to emerge along evolutionary trajectories toward improved function. Identifying the specific mechanism(s) that need to be improved upon, and tailoring our engineering efforts to each sequence, may considerably improve our chances to succeed in generating highly efficient catalysts in the future.
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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.