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Directed evolution strategies for improved enzymatic performance

Hibbert, EG; Dalby, PA; (2005) Directed evolution strategies for improved enzymatic performance. Microbial Cell Factories , 4 , Article 29. 10.1186/1475-2859-4-29. Green open access

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Abstract

The engineering of enzymes with altered activity, specificity and stability, using directed evolution techniques that mimic evolution on a laboratory timescale, is now well established. However, the general acceptance of these methods as a route to new biocatalysts for organic synthesis requires further improvement of the methods for both ease-of-use and also for obtaining more significant changes in enzyme properties than is currently possible. Recent advances in library design, and methods of random mutagenesis, combined with new screening and selection tools, continue to push forward the potential of directed evolution. For example, protein engineers are now beginning to apply the vast body of knowledge and understanding of protein structure and function, to the design of focussed directed evolution libraries, with striking results compared to the previously favoured random mutagenesis and recombination of entire genes. Significant progress in computational design techniques which mimic the experimental process of library screening is also now enabling searches of much greater regions of sequence-space for those catalytic reactions that are broadly understood and, therefore, possible to model.Biocatalysis for organic synthesis frequently makes use of whole-cells, in addition to isolated enzymes, either for a single reaction or for transformations via entire metabolic pathways. As many new whole-cell biocatalysts are being developed by metabolic engineering, the potential of directed evolution to improve these initial designs is also beginning to be realised.

Type: Article
Title: Directed evolution strategies for improved enzymatic performance
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/1475-2859-4-29
Publisher version: http://dx.doi.org/10.1186/1475-2859-4-29
Language: English
Additional information: © 2005 Hibbert and Dalby; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: Random mutagenesis libraries, In-vitro selection, Phage display, Molecular evolution, Catalytic-activity, Escherichia-coli, Computational design, Antibody library, Rapid evolution, Proteins
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Biochemical Engineering
URI: https://discovery.ucl.ac.uk/id/eprint/91505
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