By spatially isolating specific reactions, compartmentalization has allowed eukaryotic cells to achieve their high level of complexity. Artificial orthogonal compartments built via protein self-assembly might offer a similar level of control over engineered, non-native metabolic pathways for the generation of valuable products that need to be segregated from the rest of the cell. However, contrary to prokaryotes, eukaryotes do not possess proteins that can spontaneously perform such a task.
To tackle this issue, Sigmund and colleagues express the bacterial encapsulin shell and cargo protein system in human embryonic kidney cells. Even in this unfamiliar cellular environment, the system behaves as predicted, with the shell protein self-assembling into nanocompartments that encapsulate the native cargo proteins, with no apparent cytotoxicity. The system lends itself to different applications. By targeting native ferritin-like cargos the nanocompartments can sequester iron, functioning as genetically expressed contrast agents for magnetic resonance imaging, or as markers for electron microscopy. A modified version of the encapsulin nanocompartment can target destabilized proteins, shielding them from proteosomal degradation. Finally, the nanocompartments can be exploited to perform enclosed enzymatic reactions, such as the one producing melanin, a toxic metabolite used for cell imaging.