Improving enzyme properties: When are closer mutations better?

Krista L. Morley, Romas J. Kazlauskas

Research output: Contribution to journalArticlepeer-review

314 Scopus citations

Abstract

Study of mutations that improve enzyme properties reveals that in many, but not all, cases closer mutations are more effective than distant ones. For enantioselectivity, substrate selectivity and new catalytic activity (catalytic promiscuity) closer mutations improved enzymes more effectively than distant ones. However, both close and distant mutations can improve activity, thermal stability and also probably stability toward organic solvents. Typical random mutagenesis methods, such as error-prone PCR, create greater numbers of distant mutations than close mutations because enzymes contain more amino acids distant from the active site than close to the active site. This suggests that instead of mutating the entire enzyme, focusing mutations near the substrate-binding site might dramatically increase the success rate in many directed evolution experiments.

Original languageEnglish (US)
Pages (from-to)231-237
Number of pages7
JournalTrends in biotechnology
Volume23
Issue number5
DOIs
StatePublished - May 2005

Bibliographical note

Funding Information:
K.L.M. thanks the Natural Science and Engineering Research Council of Canada for a postgraduate fellowship.

Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.

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