基于生物大分子可编程多层级自组装特性, 构建新型生物催化纳米组装体

Self-assembly is a powerful method for inventing new material and new catalyst. The advantage of biological self-assembly is that it is highly programmable and has multiple-layers of regulation, and therefore it is possible to achieve multiple and complex functions. The self-assembly of carboxysome in cyanobacteria enable the carboxysome to enrich CO2 and exclude O2 in its interior, resulting in the formation of a highly efficient, multiple-enzyme catatic system. Through this important self-assembly process, efficient CO2 fixation in a O2 rich atmosphere, a highly challenging reaction, can be accomplished. This is one of the major process responsible for carbon cycling on earth. Despite its great importance, the drive force for the self-assembly into regular icosahedron, the mechanism for CO2 enrichment and O2 exclusion, and the mechanism for efficient CO2 fixation remain to be elucidated. To solve this important scientific problem, we will site-specifically incorporate chemically synthesized unnatural amino acids bearing unique IR, NMR, EPR and fluorescent functional group into carboxysome proteins. Through this strategy, we will be able to employ all kinds of physical and chemical methods to elucidate the mechanism for carboxysome self-assembly, CO2 enrichment and O2 exclusion, and high efficient CO2 fixation. We will strive to design more efficient and fuctionally diverse catalytic system than natural carboxysome. Through our investigation on carboxysome, we will build a comprehensive toolbox for protein self-assembly studies, and enable the self-assembly researchers to use proteins as versatile basic building block for self-assembly system. We will integrate the advantages of biological and chemical self-assembly, and build a golden bridge for chemistry and biological self-assembly researchers.

自组装是创造新材料、新催化剂的强大手段。生物自组装体的优势是基于其良好的可编程多层级自组装性能，能够实现较复杂的功能。蓝藻中的羧化体自组装使得在其内部富集二氧化碳，隔绝氧气，形成了多酶偶联的高效催化体系，实现了在富氧条件下的二氧化碳固定反应，是地球碳循环的主要过程之一。其自组装为正二十面体的驱动力，隔绝氧气，富集二氧化碳，高效催化二氧化碳固定的机理有待阐明。我们拟将化学合成的，具有特殊红外、核磁、顺磁、荧光性质的非天然氨基酸定点特异的引入到羧化体蛋白的特定位点，从而利用各种自组装体物理化学表征技术解析羧化体自组装机理，物质输运机理，高效催化机理，并力争设计出效率超过天然羧化体的高效催化体系。我们对羧化体展开研究，有望发展出蛋白质自组装研究的方法系统，从而以点带面，使得蛋白质成为自组装体系中可灵活使用的基本元件。我们将集成生物和化学自组装体的优势，搭建化学和生物自组装科研工作的桥梁。

自组装是创造新材料、新催化剂的强大手段。生物自组装体的优势是基于其良好的可 编程多层级自组装性能，能够实现较复杂的功能。我们利用基因密码子扩展技术将化学合成的，具有特殊红外、核磁、顺磁、荧光性质的非天然氨基酸定点特异的引入到羧化体蛋白的特定位点，从而利用各种自组装体物理化学表征技术解析羧化体自组装机理，物质输运机理，高效催化机理等。大肠杆菌体内合成了功能性α-羧化体，并验证了其功能；通过对β型羧化体壳蛋白的结构及其选择通透性机制（隔绝氧气、通透HCO3-），研究发现组装体蛋白壳确实具有一定的隔氧能力。我们通过对羧化体展开研究，发展了多种制备高度有序蛋白质组装体的新方法，并在该组装体上实现了对多酶和光捕获功能的集成, 建立了共价组装构筑二维蛋白质组装体的新策略。本项目集成了生物和化学自组装体的优势，搭建了化学和生物自组装科研工作的桥梁。