时空可控多酶催化体系的设计是人工实现各种生物学功能及生物传感器信号放大的基础。本项目针对可控多酶催化自组装体系构筑的共性科学问题如基元（酶）性质与组装体结构的关系、多基元自组装的有序结构及定位调控、组装体中酶反应耦合及传质规律展开研究。利用蛋白质分子工程设计、DNA 折纸技术、纳米界面化学修饰策略建立分子识别机制和调控弱相互作用模式，并辅以多层次及两步自组装方法，建立纳米材料/DNA 杂合架构介导的多基元（酶）有序自组装方法，分析不同空间距离及排列、酶组装方向对多酶催化级联反应的动力学影响，研究多酶组装体系的界面链式催化反应耦合、电子转移及物质传递规律，探讨构筑多步级联生物反应的多酶自组装有序结构（底物通道），实现界面酶催化级联信号放大；为定量设计和精准控制多功能集成自组装传感体系提供理论基础。

Spatiotemporally controlled self-assembly of multiple enzymes represents the useful protein immobilization technology that could catalyze whole reaction pathways much more efficiently than the same enzymes in solution. In this study, the novel methods about scaffold assisted molecular assembly for multimeric enzyme system will be developed using protein engineering, DNA origami, and nanotechnology. The catalytic efficiencies of multimeric enzyme systems will be investigated by optimizing the orientations and conformations of these enzymes and precisely controlling the spatial relationships between the components of multi-enzyme cascades. This research will be of substantial interest in a variety of sensing and biocatalytic applications based on multi-step enzyme systems.