Rational Modification Of Enzyme Structures For Enhanced Stability, Activity, And Substrate Specificity

Abstract

Enzymes are engineered extensively for biocatalysis in industrial applications, pharmaceutical processes, and synthetic biology. Rational modification of enzymes based on knowledge of mechanism and properties, therefore, remains an attractive engineering strategy. Over the past decade, significant advances have been made in engineering enzymes for three important properties: increasing global stability to improve long-term shelf-life and thermostability; enhancing catalytic activity; and modulating substrate specificity. Rational modification is often pre- and post-ceded by detailed computational analysis supported by high-throughput screening. Specific design strategies for improving stability, activity, and specificity, therefore, are discussed systematically following a description of the principles underlying enzyme function and the nature of structural modifications involved (Kunka et al., 2023).