Compartmentalisation is a fundamental feature of all living organisms. Nature organises the complex network of biochemical reactions that occur inside a cell by using compartments such as lipid organelles and large protein assemblies. In synthetic engineered cellular designs, achieving a similar level of spatial organisation is incredibly challenging.
In this presentation, I will outline our work on a family of self-assembling prokaryotic proteins known as encapsulins1, promising in vivo scaffolds for the construction of designer subcellular compartments2. We port the encapsulin system from M. xanthus3 into S. cerevisiae, creating synthetic compartments in yeast which can encapsulate any protein of interest. The encapsulation process is mediated by a short targeting peptide tag that binds the interior surface of each capsid monomer. We demonstrate that encapsulation is an effective method for extending the lifetime of unstable proteins, for bringing multiple proteins into close proximity, and for acting as nanoscale containers which can house enzymatic catalysis. In unpublished work, we have also begun to explore the fundamental effects of encapsulation on enzyme stability and kinetics.
We envisage that the capacity to build and control compartmentalised protein structures will enable us to create organelle-like functionality in synthetic cellular systems.