The SpyTag/SpyCatcher System: Precise Regulation of Covalent Conjugation and Expansion of Application Scenarios

作者：Meng‐meng Cai, Zifu Ni, Zhong‐ke Sun, Xue Li, Yanli Qi, Le Wang, Chao He, Cheng‐wei Li · 发表于：Biotechnology Journal · 年份：2025 · DOI：10.1002/biot.70131 · 被引用次数：9 · 研究领域：Biochemical and Structural Characterization、Transgenic Plants and Applications、Monoclonal and Polyclonal Antibodies Research

The SpyTag/SpyCatcher system is a modular protein assembly tool. Its core mechanism is the formation of isopeptide bonds, which achieves protein assembly through covalent coupling. This system is characterized by mild reaction conditions, rapid connection and no need for additional reagents, and shows good application potential in fields such as enzyme engineering. Although the system has made progress in application, it still faces challenges such as industrial scale and clinical immunogenicity. This paper systematically reviews the principle of the SpyTag/SpyCatcher system and its development progress. It also analyzes the deficiencies of the system in industrial applications, focuses on elaborating its specific application examples in enzyme engineering, discusses existing challenges, and looks forward to future research directions. Overall, this review aims to provide references and new ideas for research in related fields.