ArticleNature communications2021
Active-site loop variations adjust activity and selectivity of the cumene dioxygenase.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed.
- SegDesign: A modular framework for controllable protein segment engineering.Protein science : a publication of the Protein Society · 2026Article
- Designing de novo TIM barrels: insights into stabilization, diversification, and functionalization strategies.Biochemical Society transactions · 2026Review
- Regioselective Sesquiterpene Hydroxylation Directed by Tunnel Remodeling in Rieske Oxygenases.JACS Au · 2026Article
- Rieske Oxygenase-Catalyzed Biotransformations in Recombinant Cupriavidus necator Fueled by Formate Oxidation.Chembiochem : a European journal of chemical biology · 2025Article
- Rieske Oxygenases: Powerful Models for Understanding Nature's Orchestration of Electron Transfer and Oxidative Chemistry.Biochemistry · 2025Review
- Enzyme Technology in the Food Industry: Molecular Mechanisms, Applications, and Sustainable Innovations.Food science & nutrition · 2025Review
- Dynamically Interacting Protein Networks Provide a Mechanism to Overcome the Enormous Intrinsic Barrier to Orotidine 5'-Monophosphate Decarboxylation.ACS central science · 2025Article
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- β-Carotene alleviates substrate inhibition caused by asymmetric cooperativity.Nature communications · 2025Article
- Identification of Scaffold Specific Energy Transfer Networks in the Enthalpic Activation of Orotidine 5'-Monophosphate Decarboxylase.bioRxiv : the preprint server for biology · 2025Article
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- Machine learning-assisted substrate binding pocket engineering based on structural information.Briefings in bioinformatics · 2024Article
- Elucidating the Role of OACS environmental Au · 2024Article
- Targeted Mutation of a Non-catalytic Gating Residue Increases the Rate ofJournal of agricultural and food chemistry · 2023Article
- Custom tuning of Rieske oxygenase reactivity.Nature communications · 2023Article
- Chemo-Enzymatic Synthesis and Biological Assessment ofMolecules (Basel, Switzerland) · 2023Article
- Loop dynamics and the evolution of enzyme activity.Nature reviews. Chemistry · 2023Review
- Effect of Nitrogen, Air, and Oxygen on the Kinetic Stability of NAD(P)H Oxidase Exposed to a Gas-Liquid Interface.Organic process research & development · 2023Article
- Leveraging a Structural Blueprint to Rationally Engineer the Rieske Oxygenase TsaM.Biochemistry · 2023Article
- AlphaFold, allosteric, and orthosteric drug discovery: Ways forward.Drug discovery today · 2023Review
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Authors and funding
3 authors.
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Abstract
Active-site loops play essential roles in various catalytically important enzyme properties like activity, selectivity, and substrate scope. However, their high flexibility and diversity makes them challenging to incorporate into rational enzyme engineering strategies. Here, we report the engineering of hot-spots in loops of the cumene dioxygenase from Pseudomonas fluorescens IP01 with high impact on activity, regio- and enantioselectivity. Libraries based on alanine scan, sequence alignments, and deletions along with a novel insertion approach result in up to 16-fold increases in activity and the formation of novel products and enantiomers. CAVER analysis suggests possible increases in the active pocket volume and formation of new active-site tunnels, suggesting additional degrees of freedom of the substrate in the pocket. The combination of identified hot-spots with the Linker In Loop Insertion approach proves to be a valuable addition to future loop engineering approaches for enhanced biocatalysts.
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