An Inorganic Biopolymer Polyphosphate Controls Positively Charged Protein Phase Transitions

Polyphosphate (PolyP) is one of the most compact inorganic polyanionic biopolymers that participates in various physiological processes. However, the mechanism of the interaction between polyP and proteins remains poorly understood. Herein, we report that polyP can interact with positively charged green fluorescent protein, +36GFP, resulting in liquid–liquid phase separation (LLPS) by intermolecular electrostatic interactions in cells. Upon nutrient deprivation, genetically engineered Citrobacter freundii accumulates intracellular polyP at a rate of 210 μm min−1, resulting in the compartmentation of +36GFP at the cell poles within 1 h. Medium chain‐length polyP (60‐mer) could induce the formation of +36GFP coacervates in vitro at a protein concentration as low as 200 nm, which is of the same magnitude as native proteins. In contrast, shorter polyP (14‐mer) could not induce LLPS under the same conditions. This may offer a general approach to manipulate protein–protein interactions through LLPS. Crowdsurfing: An inorganic polyphosphate polymer, polyP, can interact with positively charged green fluorescent protein, +36GFP, in cells resulting in liquid–liquid phase separation (LLPS) by intermolecular electrostatic interactions. These coacervates can coalesce, demonstrating their liquid‐like properties. This may offer a general approach to manipulate protein–protein interactions through LLPS.