Biosynthesis and Reprogramming of Bacterial Organelles

自组装是自然生物系统从分子、蛋白质、细胞器到整个细胞在不同尺度上的一个基本构建过程。羧基体是所有蓝藻中发现的一种特殊的蛋白质细胞器，它固定二氧化碳并对全球二氧化碳的固定做出重要贡献。固定二氧化碳的酶Rubisco和碳酸酐酶被多个蛋白质组分覆盖的多面体蛋白质壳隔离在羧体内，作为特定分子通过的选择性渗透屏障。羧体的自组装、模块化和壳层渗透性使其成为一种特殊的系统，用于设计催化工厂和开发新的纳米材料和分子支架，目的是增强细胞新陈代谢，提高作物对二氧化碳的同化和生产力，并支持分子传递。了解自然产生的生物机器是如何合成的，对于生物技术应用中的功能生物系统的设计和合成工程至关重要。最近，我们人工合成了一种具有与天然羧基壳相似性质的羧体壳。该系统是了解羧体形成的基础和基于羧体结构的合成工程的理想选择。这个博士项目将利用微生物学、生物化学、生物物理学和合成生物学等交叉学科的方法，探索羧体壳组装和形成的分子基础，并开发体内和体外平台，将羧体壳作为新的纳米生物反应器。该项目建立在刘教授在羧体生物化学和工程、光合作用、碳同化、显微镜、合成生物学方面的专业知识，以及Howard博士在生物技术、生物工程和无细胞重构方面的专业知识，以及Marles-Wright博士在结构生物学和低温电子显微镜方面的专业知识。研究成果将为调控羧基纳米结构的生物合成以促进新陈代谢提供策略，并为新功能提供生物催化剂。

Self-assembly is a fundamental construction process of natural biological systems at different scales, ranging from molecules, proteins, organelles to the whole cell. Carboxysomes are the special protein organelles found in all cyanobacteria, which fix CO2 and contribute significantly to global CO2 fixation. The CO2-fixing enzymes Rubisco and carbonic anhydrase are sequestered within the carboxysome by a polyhedral protein shell tiled with multiple protein components, which serves as a selectively permeable barrier to the passage of specific molecules. The self-assembly, modularity, and shell permeability make carboxysomes an exceptional system for engineering catalytic factories and developing new nanomaterials and molecular scaffolds, with the aims of enhancing cellular metabolism, improving crop CO2 assimilation and productivity, and underpinning molecule delivery.Understanding how naturally occurring biological machines are synthesised is vital for the design and synthetic engineering of functional biosystems in biotechnological applications. Recently, we have generated synthetically a carboxysome shell that possesses similar properties as the native one. This system is ideal for fundamental understanding of carboxysome formation and synthetic engineering of carboxysome-based structures. Using interdisciplinary approaches including microbiology, biochemistry, biophysics, and synthetic biology, this PhD project will explore the molecular basis of the assembly and formation of carboxysome shells, and develop in vivo and in vitro platforms to engineer carboxysome shells as new nanobioreactors.This project builds on the expertise of Prof Liu in carboxysome biochemistry and engineering, photosynthesis, carbon assimilation, microscopy, synthetic biology, as well as the expertise of Dr Howard in biotechnology, bioengineering and cell-free reconstitution and Dr Marles-Wright in structural biology and cryo-electron microscopy. The research outcome will provide strategies for modulating the biosynthesis of carboxysome-based nanostructures for enhanced metabolism and biocatalysts for new functions.