Applications and insights of NMR in enzyme engineering and biocatalysis

In order to be used in biocatalysis, natural or de novo enzymes must be engineered to function under the desired reaction conditions. Rational enzyme design draws on experimental data such as structure, mechanism and sequence to identify promising hotspots, thereby reducing the number of variants th...

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Detalles Bibliográficos
Autores: Pérez, Yolanda, Moreno, Carlos J., Clapés, Pere
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2026
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/424384
Acceso en línea:http://hdl.handle.net/10261/424384
https://api.elsevier.com/content/abstract/scopus_id/105032443716
Access Level:acceso abierto
Palabra clave:Rational design
Biocatalysis
NMR
Protein engineering
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Descripción
Sumario:In order to be used in biocatalysis, natural or de novo enzymes must be engineered to function under the desired reaction conditions. Rational enzyme design draws on experimental data such as structure, mechanism and sequence to identify promising hotspots, thereby reducing the number of variants that need to be tested to improve the desired properties. Enzymes are dynamic and exist as ensembles of low-energy conformations in equilibrium with sparsely populated transient high-energy states that are often undetectable by experimental techniques targeting static native structures. Moreover, enzyme function is influenced not only by active-site residues but also by second, third, and outer-shell residues, which regulate structural dynamics and conformational sampling. Alternative conformations such as side-chain rotamers, loop rearrangements, and folding variations can enable functions like non-native ligand recognition. Historically, the incorporation of experimental structural dynamics information into enzyme engineering for abiotic catalysis was limited by the complexity and low throughput of nuclear magnetic resonance (NMR) structural analysis. This review highlights the diverse applications and emerging NMR approaches that enhance our understanding of enzyme conformational ensembles. It also covers the development of robust methodologies that allow the changes associated with the laboratory evolution of enzymes to be assessed more rapidly. These advances significantly increase NMR throughput, enabling broader applications in underutilized areas such as enzyme evolution and engineering.