Heterologous Assembly of Pleomorphic Bacterial Microcompartment Shell Architectures Spanning the Nano‐ to Microscale

Many bacteria use protein‐based organelles known as bacterial microcompartments (BMCs) to organize and sequester sequential enzymatic reactions. Regardless of their specialized metabolic function, all BMCs are delimited by a shell made of multiple structurally redundant, yet functionally diverse, hexameric (BMC‐H), pseudohexameric/trimeric (BMC‐T), or pentameric (BMC‐P) shell protein paralogs. When expressed without their native cargo, shell proteins have been shown to self‐assemble into 2D sheets, open‐ended nanotubes, and closed shells of ≈40 nm diameter that are being developed as scaffolds and nanocontainers for applications in biotechnology. Here, by leveraging a strategy for affinity‐based purification, it is demonstrated that a wide range of empty synthetic shells, many differing in end‐cap structures, can be derived from a glycyl radical enzyme‐associated microcompartment. The range of pleomorphic shells observed, which span ≈2 orders of magnitude in size from ≈25 nm to ≈1.8 µm, reveal the remarkable plasticity of BMC‐based biomaterials. In addition, new capped nanotube and nanocone morphologies are observed that are consistent with a multicomponent geometric model in which architectural principles are shared among asymmetric carbon, viral protein, and BMC‐based structures. Self‐assembling shell proteins derived from bacterial microcompartments are a promising new biomaterial with applications in drug delivery, metabolic engineering, cell‐free synthesis, and bioelectronics. A synthetic platform produces pleomorphic shells spanning the nano‐ to microscale that are rapidly purified. Geometric models of new morphologies suggest shared design principles with asymmetric carbon and viral protein analogs.