Organizing Enzymes on Self‐Assembled Protein Cages for Cascade Reactions

作者：Wei Kang, Xiao Ma, Deepika Kakarla, Huawei Zhang, Yunming Fang, Baizhu Chen, Kongfu Zhu, Danni Zheng, Zhiyue Wu, Bo Li, Chuang Xue · 发表于：Angewandte Chemie International Edition · 年份：2022 · DOI：10.1002/anie.202214001 · 被引用次数：45 · 研究领域：Glycosylation and Glycoproteins Research、RNA and protein synthesis mechanisms、Monoclonal and Polyclonal Antibodies Research

Abstract Cells use self‐assembled biomaterials such as lipid membranes or proteinaceous shells to coordinate thousands of reactions that simultaneously take place within crowded spaces. However, mimicking such spatial organization for synthetic applications in engineered systems remains a challenge, resulting in inferior catalytic efficiency. In this work, we show that protein cages as an ideal scaffold to organize enzymes to enhance cascade reactions both in vitro and in living cells. We demonstrate that not only enzyme‐enzyme distance but also the improved K m value contribute to the enhanced reaction rate of cascade reactions. Three sequential enzymes for lycopene biosynthesis have been co‐localized on the exterior of the engineered protein cages in Escherichia coli , leading to an 8.5‐fold increase of lycopene production by streamlining metabolic flux towards its biosynthesis. This versatile system offers a powerful tool to achieve enzyme spatial organization for broad applications in biocatalysis.