Compartmentalization at the nanoscale is fundamental in nature, where the spatial segregation of biochemical reactions within cells ensures optimal conditions for regulating metabolic pathways. Here, we present a nature-inspired approach to engineer enzymatic cascade reactions taking place between separate vesicular nanocompartments (polymersomes), each containing one enzyme type. We propose, by the selected combination of enzymes, an efficient solution to detoxify the harmful effect of uric acid and prevent the accumulation of the derived H₂O₂, both being associated with various pathological conditions (e.g., gout and oxidative stress). Fungal uricase and horseradish peroxidase combined to act in tandem, and they were separately encapsulated within nanocompartments that were equipped with channel porins as gates to allow passage of substrates and products from each step of the reaction. We established the molecular factors affecting the efficiency of the overall reaction, and the protective role of the compartments. Interestingly, the cascade reaction between separate nanocompartments was as efficient as for free enzymes in complex media, such as human serum. The nanocompartments were nontoxic toward cells, and more importantly, addition of the tandem catalytic nanocompartments to cells exposed to uric acid provided simultaneous detoxification of uric acid and the H₂O₂. Such catalytic nanocompartments can be used as a platform for understanding fundamental factors affecting intracellular communication and can introduce non-native metabolic reactions into living systems for therapeutic applications.

中文翻译：

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串联串联支持级联反应的纳米级酶区室。

纳米级的分隔是自然界的基础，细胞内生化反应的空间隔离确保了调节代谢途径的最佳条件。在这里，我们提出了一种自然界启发的方法来工程化各个独立的囊泡纳米隔室（聚合物囊泡）之间发生的酶促级联反应，每种囊泡均包含一种酶类型。我们建议通过选择酶的组合，为排解尿酸的有害作用并防止衍生的H ₂ O ₂的积聚提供一种有效的解决方案。，都与各种病理状况（例如痛风和氧化应激）有关。真菌尿酸酶和辣根过氧化物酶组合起串联作用，并将它们分别包裹在装有通道孔蛋白作为门的纳米隔室中，以允许反应的每个步骤中的底物和产物通过。我们建立了影响整个反应效率以及隔室保护作用的分子因素。有趣的是，分离的纳米隔室之间的级联反应与复杂介质（例如人血清）中的游离酶一样有效。纳米隔室对细胞无毒，更重要的是，向暴露于尿酸的细胞中添加串联催化纳米隔室可同时使尿酸和氢解毒₂ O ₂。这样的催化纳米隔室可以用作理解影响细胞内通讯的基本因素的平台，并且可以将非天然代谢反应引入用于治疗应用的生命系统。