Rational design of enzyme activity and enantioselectivity

Zhongdi Song; Qunfeng Zhang; Wenhui Wu; Zhongji Pu; Haoran Yu

doi:10.3389/fbioe.2023.1129149

Rational design of enzyme activity and enantioselectivity

Front Bioeng Biotechnol. 2023 Jan 24:11:1129149. doi: 10.3389/fbioe.2023.1129149. eCollection 2023.

Authors

Zhongdi Song¹, Qunfeng Zhang², Wenhui Wu³, Zhongji Pu^{2

3}, Haoran Yu^{2

3}

Affiliations

¹ Key Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province, Interdisciplinary Research Academy, Zhejiang Shuren University, Hangzhou, China.
² Institute of Bioengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, Zhejiang, China.
³ ZJU-Hangzhou Global Scientific and Technological Innovation Centre, Hangzhou, Zhejiang, China.

Abstract

The strategy of rational design to engineer enzymes is to predict the potential mutants based on the understanding of the relationships between protein structure and function, and subsequently introduce the mutations using the site-directed mutagenesis. Rational design methods are universal, relatively fast and have the potential to be developed into algorithms that can quantitatively predict the performance of the designed sequences. Compared to the protein stability, it was more challenging to design an enzyme with improved activity or selectivity, due to the complexity of enzyme molecular structure and inadequate understanding of the relationships between enzyme structures and functions. However, with the development of computational force, advanced algorithm and a deeper understanding of enzyme catalytic mechanisms, rational design could significantly simplify the process of engineering enzyme functions and the number of studies applying rational design strategy has been increasing. Here, we reviewed the recent advances of applying the rational design strategy to engineer enzyme functions including activity and enantioselectivity. Five strategies including multiple sequence alignment, strategy based on steric hindrance, strategy based on remodeling interaction network, strategy based on dynamics modification and computational protein design are discussed and the successful cases using these strategies are introduced.

Keywords: biocatalysis; enzyme activity; enzyme enantioselectivity; enzyme engineering; rational design.

Publication types

Review

Grants and funding

This work was supported by the Scientific Research Start-up Program of Zhejiang Shuren University (Grant No. 2021R009), the Scientific Research Program of Zhejiang Provincial Education Department (Grant No. Y202147851), the National Natural Science Foundation of China (Grant No. 22108245), the Key Research and Development Program of China (Grant No. 2022YFA0913000) and the Fundamental Research Funds for the Central Universities (Grant No. 226-2022-00214).