Phase separation in synthetic biology

Abstract

Background: The concept of phase separation has been used to describe and interpret physicochemical phenomena in biological systems for decades. Many intracellular macromolecules undergo phase separation, where it plays important roles in gene regulation, cellular signaling, metabolic reactions and so on, due to its unique dynamic properties and biological effects. As the noticeable importance of phase separation, pioneer researchers have explored the possibility to introduce the synthetically engineered phase separation for applicable cell function.

Results: In this article, we illustrated the application value of phase separation in synthetic biology. We described main states of phase separation in detail, summarized some ways to implement synthetic condensates and several methods to regulate phase separation, and provided a substantial amount of identical examples to illuminate the applications and perspectives of phase separation in synthetic biology.

Conclusions: Multivalent interactions implement phase separation in synthetic biology. Small molecules, light control and spontaneous interactions induce and regulate phase separation. The synthetic condensates are widely used in signal amplifications, designer orthogonally non-membrane-bound organelles, metabolic pathways, gene regulations, signaling transductions and controllable platforms. Studies on quantitative analysis, more standardized modules and precise spatiotemporal control of synthetic phase separation may promote the further development of this field.

Author summary

A substantial amount of physical theories and biological experiments have been developed to uncover the underlying principles of phase separation in biology. The synthetic condensates through phase separation have been used to implement many specific functions in biological systems. In the future, more biomedical functions related to phase separation can be explored, more diseases triggered or accelerated by phase separation may be treated better, more artificial applications can be realized by synthetic condensates.

Graphical abstract

Keywords

phase separation / synthetic biology / multivalent interaction / non-membrane-bound organelle / signaling transduction and amplification

References

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ACKNOWLEDGEMENTS

Works presented by Peking 2018 team in International Genetically Engineered Machine (iGEM) competition inspire this article. We thank Cheng Li, Xin Li, Chunfeng Zhang and Ziheng Zhao from Peking University for their assistance. This work was supported by the National Key Basic Research Program of China 2018YFA0902800 (P.W.) and the National Natural Science Foundation of China 31470819 (P.W.), 31622022 (P.W.).

COMPLIANCE WITH ETHICS GUIDELINES

The authors Shuyu Shi, Wen Si, Xiaoyi Ouyang and Ping Wei declare that they have no conflict of interests. This article is a review article and does not contain any studies with human or animal subjects performed by any of the authors.

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