Semi-rational approaches to engineering enzyme activity: combining the benefits of directed evolution and rational design

Many research groups successfully rely on whole-gene random mutagenesis and recombination approaches for the directed evolution of enzymes. Recent advances in enzyme engineering have used a combination of these random methods of directed evolution with elements of rational enzyme modification to suc...

Full description

Saved in:
Bibliographic Details
Published in:Current opinion in biotechnology 2005-08, Vol.16 (4), p.378-384
Main Authors: Chica, Roberto A, Doucet, Nicolas, Pelletier, Joelle N
Format: Article
Language:English
Subjects:
Combinatorial Chemistry Techniques
Computational Biology
Directed Molecular Evolution
Enzymes - genetics
Enzymes - physiology
Protein Engineering
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Many research groups successfully rely on whole-gene random mutagenesis and recombination approaches for the directed evolution of enzymes. Recent advances in enzyme engineering have used a combination of these random methods of directed evolution with elements of rational enzyme modification to successfully by-pass certain limitations of both directed evolution and rational design. Semi-rational approaches that target multiple, specific residues to mutate on the basis of prior structural or functional knowledge create ‘smart’ libraries that are more likely to yield positive results. Efficient sampling of mutations likely to affect enzyme function has been conducted both experimentally and, on a much greater scale, computationally, with remarkable improvements in substrate selectivity and specificity and in the de novo design of enzyme activities within scaffolds of known structure.
ISSN:0958-1669
1879-0429
DOI:10.1016/j.copbio.2005.06.004