蛋白质自组装机器在人工多酶复合体系中的研究与应用进展

Advances of self-assembly protein molecular machines in artificial multienzyme complexes

随着合成生物学的研究与发展,人们利用微生物细胞或无细胞体系对代谢途径中的多酶体系进行编程和重组,成功合成了大量的功能化合物。但由于多酶体系分散度高,造成体系代谢流速和流量不平衡,代谢效率和产量降低。生物体内存在多种天然的多酶自组装复合体,如纤维素小体机器、细胞信号转导中的激酶级联通路等。研究表明,这些体系中存在的底物通道效应和协同作用机制是多酶复合体具有高催化效率的原因。模拟和借鉴天然多酶体系,并结合生物体中蛋白质与DNA、RNA等相互作用设计和构建人工自组装多酶体系,是提高代谢效率的重要途径。现对蛋白质自组装机器在人工多酶体系中的研究进展进行综述。

With the development of synthetic biology, reprograming multienzyme complex and forming novel metabolic pathways to produce biocommodities have been carried out in microbial cell factories or cell-free systems. engineered metabolic pathways constructed from enzymes heterologous to the production host often suffer from flux imbalances, resulting in lower metabolic efficiency and product titers, as they typically lack the regulatory mechanisms characteristic of natural metabolism which can be controlled accurately. Natural multienzymes complexes, such as cellulosomes and the kinase cascade from the intracellular signal transduction, display higher catalytic efficiency because of the substrate channeling and synergy effect between different enymes. Inspired by natural systems, designing and constructing self-assembly artificial multienzyme complexes by using the macromoleculars is a promising method to balance the flux and enhance metabolic efficiency. in this paper, we introduced the advances of self-assembly protein molecular machines in artificial multienzyme complexes. We try to provide a framework for the future design and construction of multienzyme system.