Improving enzyme properties: when are closer mutations better?

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.

journal_name

Trends Biotechnol

journal_title

Trends in biotechnology

authors

Morley KL,Kazlauskas RJ

doi

10.1016/j.tibtech.2005.03.005

subject

Has Abstract

pub_date

2005-05-01 00:00:00

pages

231-7

issue

5

eissn

0167-7799

issn

1879-3096

pii

S0167-7799(05)00077-6

journal_volume

23

pub_type

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