Liquid-liquid phase separation (LLPS) in synthetic biosystems

In living systems, there is emerging evidence that nature uses liquid-liquid phase separation (LLPS) to organize diverse cellular processes such as signal transduction, translation regulation, and gene expression among chemical chaos. Inspired by the naturally occurring LLPS, there is increasing interest in the deployment of LLPS in synthetic biosystems towards a wide range of applications. Although much progress has been made, there is still a limited understanding of LLPS in synthetic biosystems. Importantly, studies in LLPS in non-living systems (i.e., polymer systems) and in living systems have been progressed separately. There is an urgent need to summarize and integrate our current understanding of LLPS in different systems to inform the design of artificial LLPS in synthetic biosystems. In this review, we first summarize the development of theoretical modeling of LLPS in non-living systems and living systems. We then explore current approaches for the construction and functionalization of LLPS in synthetic biosystems. We finally review the state of the art of LLPS in synthetic biosystems towards applications in synthetic biology, cellular engineering and biotechnology.