ReviewProceedings of the National Academy of Sciences of the United States of America2009
In the light of directed evolution: pathways of adaptive protein evolution.
Review in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 207 papers.
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207 citing papers in PubMed.
- Application and Molecular Modification of Enzyme in Textile Degumming.Applied biochemistry and biotechnology · 2026Review
- High-throughput Optical Analysis to Inform Design of Electrochemical Biosensors.ACS measurement science au · 2026Review
- How far can you go? Extrapolating values of catalytic activity from known protein landscapes in natural and directed evolution.Chemical Society reviews · 2026Review
- Functional conservation with mechanistic drift: AMP activation in the evolution of archaeal sugar kinases.Molecular biology and evolution · 2026Article
- Harnessing Nature's Algorithm: From Test Tubes to Autonomous In Vivo Evolution.Biotechnology journal · 2026Review
- Synthetic Biology Approaches to Enzymology in Food and Agriculture Systems.Journal of agricultural and food chemistry · 2026Review
- Self-assembling protein cages: from coiled-coil module to machine learning-drivenMaterials advances · 2026Review
- Factors controlling protein evolvability-at the molecular scale.European biophysics journal : EBJ · 2026Article
- A Comprehensive Review on Steviol Glycosides: Sources, Properties, Bioactivities, Sensory-Functional Enhancement and Bioproduction Strategies.Plants (Basel, Switzerland) · 2026Review
- Examining selection dynamics and limitations in multi-round protein selection of high diversity libraries.Protein engineering, design & selection : PEDS · 2026Article
- Episodic positive selection structurally stabilizes the Arabidopsis CONSTANS-like gene COL5 indicating adaptive evolution.Scientific reports · 2026Article
- AI-Driven Enzyme Engineering: Emerging Models and Next-Generation Biotechnological Applications.Molecules (Basel, Switzerland) · 2025Review
- Ancestral Sequence Reconstruction to Accelerate Non-heme Iron-dependent Biocatalyst Engineering.ACS central science · 2025Article
- Directed evolution of a beta-lactamase samples a wide variety of conformational states.Protein science : a publication of the Protein Society · 2025Article
- Article
- Directed evolution of hydrocarbon-producing enzymes.Biotechnology for biofuels and bioproducts · 2025Review
- Mining Thermophile Genomes for New PETases with Exceptional Thermostabilities Using Sequence Similarity Networks.Chembiochem : a European journal of chemical biology · 2025Article
- Thermal Adaptation of Cytosolic Malate Dehydrogenase Revealed by Deep Learning and Coevolutionary Analysis.Journal of chemical theory and computation · 2025Article
- DEKP: a deep learning model for enzyme kinetic parameter prediction based on pretrained models and graph neural networks.Briefings in bioinformatics · 2025Article
- Artificial Intelligence-Based Approaches for AAV Vector Engineering.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
147 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Directed evolution is a widely-used engineering strategy for improving the stabilities or biochemical functions of proteins by repeated rounds of mutation and selection. These experiments offer empirical lessons about how proteins evolve in the face of clearly-defined laboratory selection pressures. Directed evolution has revealed that single amino acid mutations can enhance properties such as catalytic activity or stability and that adaptation can often occur through pathways consisting of sequential beneficial mutations. When there are no single mutations that improve a particular protein property experiments always find a wealth of mutations that are neutral with respect to the laboratory-defined measure of fitness. These neutral mutations can open new adaptive pathways by at least 2 different mechanisms. Functionally-neutral mutations can enhance a protein's stability, thereby increasing its tolerance for subsequent functionally beneficial but destabilizing mutations. They can also lead to changes in "promiscuous" functions that are not currently under selective pressure, but can subsequently become the starting points for the adaptive evolution of new functions. These lessons about the coupling between adaptive and neutral protein evolution in the laboratory offer insight into the evolution of proteins in nature.
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