Biomolecular condensates concentrate macromolecules into discrete cellular foci without an encapsulating membrane. Condensates are often presumed to increase enzymatic reaction rates through increased concentrations of enzymes and substrates (mass action), although this idea has not been widely tested and other mechanisms of modulation are possible. Here we describe a synthetic system where the SUMOylation enzyme cascade is recruited into engineered condensates generated by liquid-liquid phase separation of multidomain scaffolding proteins. SUMOylation rates can be increased up to 36-fold in these droplets compared to the surrounding bulk, depending on substrate KM. This dependency produces substantial specificity among different substrates. Analyses of reactions above and below the phase separation threshold lead to a quantitative model in which reactions in condensates are accelerated by mass action and by changes in substrate KM, likely due to scaffold-induced molecular organization. Thus, condensates can modulate reaction rates both by concentrating molecules and by physically organizing them.

中文翻译：

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相分离可通过浓度和分子组织提高酶的活性

生物分子缩合物将大分子浓缩成离散的细胞灶，而没有包膜。通常认为，冷凝物会通过增加酶和底物的浓度（质量作用）来提高酶的反应速率，尽管这一想法尚未得到广泛测试，并且其他调节机制也是可能的。在这里，我们描述了一个合成系统，其中SUMOylation酶级联被募集到通过多域支架蛋白的液-液相分离产生的工程凝析物中。与周围的块体相比，这些液滴的SUMOylation速率最多可提高36倍，具体取决于底物KM。这种依赖性在不同底物之间产生了实质性的特异性。对高于和低于相分离阈值的反应进行分析得出了定量模型，其中冷凝物中的反应可能通过质量作用和底物KM的变化而加速，这可能是由于支架诱导的分子组织所致。因此，缩合物可以通过浓缩分子和通过物理组织分子来调节反应速率。