ArticleProceedings of the National Academy of Sciences of the United States of America2014
Engineering of an epoxide hydrolase for efficient bioresolution of bulky pharmaco substrates.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 92 citations in OpenAlex.
- Tailoring Regioselectivity-Controlled UDP-Glycosyltransferase for Bidirectional Glycosylation of Tyrosol via Free Energy-Driven Pocket Reshaping and Tunnel Engineering.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Symmetric Ligand Binding Pathways and Dual-State Bottleneck in [NiFe] Hydrogenases from Unbiased Molecular Dynamics.The journal of physical chemistry letters · 2025Article
- PathInHydro, a Set of Machine Learning Models to Identify Unbinding Pathways of Gas Molecules in [NiFe] Hydrogenases.Journal of chemical information and modeling · 2025Article
- Article
- Enhancing β-Galactosidase Performance for Galactooligosaccharides Preparation via Strategic Glucose Re-Tunneling.International journal of molecular sciences · 2024Article
- Geometric Remodeling of Nitrilase Active Pocket Based on ALF-Scanning Strategy To Enhance Aromatic Nitrile Substrate Preference and Catalytic Efficiency.Applied and environmental microbiology · 2023Article
- Epoxide Hydrolases: Multipotential Biocatalysts.International journal of molecular sciences · 2023Review
- Rational design of enzyme activity and enantioselectivity.Frontiers in bioengineering and biotechnology · 2023Review
- Geometry-Based versus Small-Molecule Tracking Method for Tunnel Identification: Benefits and Pitfalls.Journal of chemical information and modeling · 2022Article
- Evolution of tunnels in α/β-hydrolase fold proteins-What can we learn from studying epoxide hydrolases?PLoS computational biology · 2022Article
- Biochemical Characterization and Cold-Adaption Mechanism of a PL-17 Family Alginate Lyase Aly23 from Marine BacteriumMarine drugs · 2022Article
- Structure-function relationship between soluble epoxide hydrolases structure and their tunnel network.Computational and structural biotechnology journal · 2022Article
- Redesigning Enzymes for Biocatalysis: Exploiting Structural Understanding for Improved Selectivity.Frontiers in molecular biosciences · 2022Review
- Design of a Microbial Remediation Inoculation Program for Petroleum Hydrocarbon Contaminated Sites Based on Degradation Pathways.International journal of environmental research and public health · 2021Article
- Machine Learning Enables Selection of Epistatic Enzyme Mutants for Stability Against Unfolding and Detrimental Aggregation.Chembiochem : a European journal of chemical biology · 2021Article
- Mutation of an atypical oxirane oxyanion hole improves regioselectivity of the α/β-fold epoxide hydrolase Alp1U.The Journal of biological chemistry · 2020Article
- Plant growth-promoting activities and genomic analysis of the stress-resistantBiotechnology reports (Amsterdam, Netherlands) · 2020Article
- Directed evolution methods for overcoming trade-offs between protein activity and stability.AIChE journal. American Institute of Chemical Engineers · 2020Article
- Characterization and Application of an Alginate Lyase, Aly1281 from Marine BacteriumMarine drugs · 2020Article
- Substantially improving the enantioconvergence of PvEH1, a Phaseolus vulgaris epoxide hydrolase, towards m-chlorostyrene oxide by laboratory evolution.Microbial cell factories · 2019Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Optically pure epoxides are essential chiral precursors for the production of (S)-propranolol, (S)-alprenolol, and other β-adrenergic receptor blocking drugs. Although the enzymatic production of these bulky epoxides has proven difficult, here we report a method to effectively improve the activity of BmEH, an epoxide hydrolase from Bacillus megaterium ECU1001 toward α-naphthyl glycidyl ether, the precursor of (S)-propranolol, by eliminating the steric hindrance near the potential product-release site. Using X-ray crystallography, mass spectrum, and molecular dynamics calculations, we have identified an active tunnel for substrate access and product release of this enzyme. The crystal structures revealed that there is an independent product-release site in BmEH that was not included in other reported epoxide hydrolase structures. By alanine scanning, two mutants, F128A and M145A, targeted to expand the potential product-release site displayed 42 and 25 times higher activities toward α-naphthyl glycidyl ether than the wild-type enzyme, respectively. These results show great promise for structure-based rational design in improving the catalytic efficiency of industrial enzymes for bulky substrates.
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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.