Molecular principles for the biogenesis and assemble of carboxysomes

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.