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Synthetic protein condensates for cellular and metabolic engineering

Abstract

Protein condensates are distinct structures assembled in living cells that concentrate molecules via phase separation in a confined subcellular compartment. In the past decade, remarkable advances have been made to discover the fundamental roles of the condensates in spatiotemporal control of cellular metabolism and physiology and to reveal the molecular principles, components and driving forces that underlie their formation. Here we review the unique properties of the condensates, the promise and hurdles for harnessing them toward purposeful design and manipulation of biological functions in living cells. In particular, we highlight recent advances in mining and understanding the proteinaceous components for creating designer condensates, along with the engineering approaches to manipulate their material properties and biological functions. With these advances, a greater variety of complex organelle-like structures can be built for diverse applications, with unprecedented effects on synthetic biology.

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Fig. 1: Different types of protein condensate.
Fig. 2: Building blocks of synthetic protein condensates.
Fig. 3: Tools for controlling synthetic protein condensates in cells.
Fig. 4: Synthetic protein condensates for cellular engineering.
Fig. 5: Synthetic condensates for metabolic engineering.

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Acknowledgements

This work is supported by the National Key Research and Development Program of China (grants 2020YFA0907702 and 2021YFA0909502 to X.-X.X.), the National Natural Science Foundation of China (grant 32071414 to X.-X.X. and grants 32270107 and 22075179 to Z.-G.Q.) and the Natural Science Foundation of Shanghai (grant 21ZR1432100 to Z.-G.Q.).

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X.-X.X. and Z.-G.Q. conceived of the manuscript. Z.-G.Q. and X.-X.X. wrote the paper. S.-C.H. reviewed the literature and edited the paper.

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Correspondence to Xiao-Xia Xia.

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Qian, ZG., Huang, SC. & Xia, XX. Synthetic protein condensates for cellular and metabolic engineering. Nat Chem Biol 18, 1330–1340 (2022). https://doi.org/10.1038/s41589-022-01203-3

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