Molecular principles for the biogenesis and assemble of carboxysomes

细胞器将特定的生化途径限制在细胞内，以提高代谢效率，减轻代谢串扰，并促进隔离途径的时空调节。羧基体是细菌的微区室，作为一个原始的蛋白质为基础的细胞器，用于CO2固定。它将关键的CO2固定酶Rubisco和碳酸酐酶封装在半透性蛋白质壳内。这种精心设计的结构在Rubisco周围提供了升高的CO2水平，以增强碳固定。碳氧体主要存在于海洋蓝藻和许多变形菌中，对全球初级生产力有重要贡献。尽管它在全球范围内的重要性，我们的知识如何产生的α-羧基体和功能维持在细菌细胞是令人惊讶的有限。该博士项目旨在研究自养微生物中羧基体原位生物合成，组装和调控的分子原理，使用分子遗传学，生物化学，高分辨率显微成像，结构生物学和合成生物学的多学科技术。通过表征天然和合成形式的各种carboxysomes的结构和功能特性，该项目将以前所未有的细节阐明carboxysomes如何在细胞中形成和功能调节以实现功能，以及来自不同生物体的carboxysomes的多样性。对微区室自组装和功能性的深入了解将为使用合成生物学的代谢细胞器的生物工程以及用于各种生物技术应用的新纳米材料和蛋白质支架的开发提供信息。

Organelles confine specific biochemical pathways within the cell to enhance metabolic efficiency, alleviate metabolic crosstalk, and facilitate spaciotemporal regulation of sequestered pathways. The carboxysome is a bacterial microcompartment that functions as a primitive protein-based organelle for CO2 fixation. It encapsulates the key CO2-fixing enzymes, Rubisco and carbonic anhydrase, within a semi-permeable protein shell. This elaborate architecture provides elevated CO2 levels around Rubisco for enhanced carbon fixation. The carboxysome is predominantly in oceanic cyanobacteria and many proteobacteria, and makes a great contribution to global primary productivity. Despite its importance on the global scale, our knowledge about how the a-carboxysome is generated and functionally maintained in bacterial cells is surprisingly limited. This PhD project is aimed at studying the molecular principles underlying the in situ biosynthesis, assembly, and regulation of carboxysomes in autotrophic microorganisms, using multidisciplinary techniques of molecular genetics, biochemistry, high-resolution microscopic imaging, structural biology, and synthetic biology. By characterising the architectural and functional properties of various carboxysomes in the native and synthetic forms, this project will elucidate in unprecedented detail how carboxysomes are formed and functionally modulated in cells to fulfil functions, and the diversity of carboxysomes from different organisms in specific niches. Advanced understanding of microcompartment self-assembly and functionality will inform bioengineering of metabolic organelles using synthetic biology and development of new nanomaterials and protein scaffolds for diverse biotechnological applications.