ArticleProceedings of the National Academy of Sciences of the United States of America2004
Controlling the enantioselectivity of enzymes by directed evolution: practical and theoretical ramifications.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed.
- Electrostatic potential as a reactivity scoring function in computer-assisted enzyme engineering.The FEBS journal · 2025Article
- Promiscuity Guided Evolution of Decarboxylative Aldolases for Synthesis of Tertiary γ-Hydroxy Amino Acids.Angewandte Chemie (International ed. in English) · 2025Article
- Advances in the Directed Evolution of Computer-aided Enzymes.Current topics in medicinal chemistry · 2025Review
- A Dynamic Loop in Halohydrin Dehalogenase HheG Regulates Activity and Enantioselectivity in Epoxide Ring Opening.ACS catalysis · 2024Article
- The astrochemical evolutionary traits of phospholipid membrane homochirality.Nature reviews. Chemistry · 2024Review
- EnzymeMap: curation, validation and data-driven prediction of enzymatic reactions.Chemical science · 2023Article
- Chiral recognition of neutral guests by chiral naphthotubes with a bis-thiourea endo-functionalized cavity.Nature communications · 2023Article
- Computer-assisted multistep chemoenzymatic retrosynthesis using a chemical synthesis planner.Chemical science · 2023Article
- Evolutionary Engineering of a Cp*Rh(III) Complex-Linked Artificial Metalloenzyme with a Chimeric β-Barrel Protein Scaffold.Journal of the American Chemical Society · 2023Article
- Resolving Enantiomers of 2-Hydroxy Acids by Nuclear Magnetic Resonance.Analytical chemistry · 2022Article
- Similarity based enzymatic retrosynthesis.Chemical science · 2022Article
- Directed Evolution of a Cp*RhChembiochem : a European journal of chemical biology · 2021Article
- A Machine Learning Study on the Thermostability Prediction of (R)-BioMed research international · 2021Article
- Folding Assessment of Incorporation of Noncanonical Amino Acids Facilitates Expansion of Functional-Group Diversity for Enzyme Engineering.Chemistry (Weinheim an der Bergstrasse, Germany) · 2020Article
- Structural and catalytic effects of surface loop-helix transplantation within haloalkane dehalogenase family.Computational and structural biotechnology journal · 2020Article
- Directed Evolution ofFrontiers in bioengineering and biotechnology · 2020Article
- Hydroxyl Radical-Coupled Electron-Transfer Mechanism of Flavin-Dependent Hydroxylases.The journal of physical chemistry. B · 2019Article
- Machine learning-assisted directed protein evolution with combinatorial libraries.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Boosting the efficiency of site-saturation mutagenesis for a difficult-to-randomize gene by a two-step PCR strategy.Applied microbiology and biotechnology · 2018Article
- Rational and Semirational Protein Design.Methods in molecular biology (Clifton, N.J.) · 2018Review
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1 author.
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Abstract
A fundamentally new approach to asymmetric catalysis in organic chemistry is described based on the in vitro evolution of enantioselective enzymes. It comprises the appropriate combination of gene mutagenesis and expression coupled with an efficient high-throughput screening system for evaluating enantioselectivity (enantiomeric excess assay). Several such cycles lead to a "Darwinistic" process, which is independent of any knowledge concerning the structure or the mechanism of the enzyme being evolved. The challenge is to choose the optimal mutagenesis methods to navigate efficiently in protein sequence space. As a first example, the combination of error-prone mutagenesis, saturation mutagenesis, and DNA-shuffling led to a dramatic enhancement of enantioselectivity of a lipase acting as a catalyst in the kinetic resolution of a chiral ester. Mutations at positions remote from the catalytically active center were identified, a surprising finding, which was explained on the basis of a novel relay mechanism. The scope and limitations of the method are discussed, including the prospect of directed evolution of stereoselective hybrid catalysts composed of robust protein hosts in which transition metal centers have been implanted.
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