Design Principles of Protein Organelles

Cells use structure to catalyze and facilitate the chemical reactions of metabolism. This principle is embodied by bacterial microcompartments, a class of protein-based organelles that are found in nearly 30% of bacterial genomes. More specifically, microcompartments are capsid-like structures composed of thousands of proteins that self-assemble to form an outer shell and encapsulated cargo proteins that form a short metabolic pathway within the inner lumen. Despite knowledge of the component proteins, it is less well understood how these structures self-assemble and function in vivo. Here, we describe our efforts to answer these questions using a combination of synthetic expression in heterologous hosts, modeling of the reaction-diffusion process, and biochemical reconstitution of assembly. These results suggest general themes for how encapsulation can improve pathway performance and specific methods for employing microcompartments and other capsid-forming proteins as a means of engineering metabolism and biomaterials.