Fig. 3

Application of higher-order protein assembly in synthetic biology. a Synthetic membraneless organelles, formed using proteins that undergo phase separation, can be used to enforce orthogonality of regulatory connections and biochemical reactions. This principle was recently used to create synthetic orthogonally translating (OT) organelles as sites for producing proteins that incorporate unnatural amino acids. b Exacting control over the formation of intracellular protein assemblies using optoDroplets. In this scheme, IDRs fused to light-inducible oligomerization domains enable the induction of phase separation by illumination with light. c Protein assembly systems as the basis of sensing and signal processing devices. Left: Protein assemblies can undergo dramatic changes in structure in response to small variations in environmental conditions, enabling exquisite sensing capabilities. Right: Changes in aggregation can be used to control downstream cellular processes. In the yTRAP system, the solubility state of an assembly domain is coupled to the activity of a synthetic TF and consequent activation of GOIs. d Prion proteins can exist stably in distinct conformational states, offering the potential to create synthetic memory devices based on prion switching