Work

Computational Thermostabilization of an Enzyme

Year: 2005

Type: article

Abstract: Thermostabilizing an enzyme while maintaining its activity for industrial or biomedical applications can be difficult with traditional selection methods. We describe a rapid computational approach that identified three mutations within a model enzyme that produced a 10 degrees C increase in apparent melting temperature T(m) and a 30-fold increase in half-life at 50 degrees C, with no reduction in catalytic efficiency. The effects of the mutations were synergistic, giving an increase in excess of the sum of their individual effects. The redesigned enzyme induced an increased, temperature-dependent bacterial growth rate under conditions that required its activity, thereby coupling molecular and metabolic engineering.

Source: Science

DOI: 10.1126/science.1107387

Authors: Aaron Korkegian, Margaret E. Black, David Baker, Barry L. Stoddard

Institutions: Howard Hughes Medical Institute, University of Washington, Fred Hutch Cancer Center, Washington State University

Language: English

Topic: Enzyme Catalysis and Immobilization

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funders: National Cancer Institute, National Institute of General Medical Sciences