Subcellular compartmentalization of macromolecules increases flux and prevents inhibitory interactions to control biochemical reactions. Inspired by this functionality, we sought to build designer compartments that function as hubs to regulate the flow of information through cellular control systems. We report a synthetic membraneless organelle platform to control endogenous cellular activities through sequestration and insulation of native proteins. We engineer and express a disordered protein scaffold to assemble micron-size condensates and recruit endogenous clients via genomic tagging with high-affinity dimerization motifs. By relocalizing up to 90% of targeted enzymes to synthetic condensates, we efficiently control cellular behaviors, including proliferation, division and cytoskeletal organization. Further, we demonstrate multiple strategies for controlled cargo release from condensates to switch cells between functional states. These synthetic organelles offer a powerful and generalizable approach to modularly control cell decision-making in a variety of model systems with broad applications for cellular engineering.

大分子的亚细胞区室化增加通量并防止抑制性相互作用以控制生化反应。受此功能的启发，我们试图构建设计师隔间，作为枢纽来调节通过蜂窝控制系统的信息流。我们报告了一种合成无膜细胞器平台，通过隔离和隔离天然蛋白质来控制内源性细胞活动。我们设计并表达了一个无序的蛋白质支架来组装微米级的缩合物，并通过具有高亲和力二聚化基序的基因组标记来招募内源性客户。通过将高达 90% 的靶向酶重新定位为合成缩合物，我们有效地控制了细胞行为，包括增殖、分裂和细胞骨架组织。更远，我们展示了多种策略来控制从冷凝物中释放货物以在功能状态之间切换细胞。这些合成细胞器提供了一种强大且可通用的方法来模块化控制各种模型系统中的细胞决策，这些模型系统具有广泛的细胞工程应用。