Natural multi-osmolyte cocktails form deep eutectic systems of unprecedented complexity: discovery, affordances and perspectives,Green Chemistry

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Natural multi-osmolyte cocktails form deep eutectic systems of unprecedented complexity: discovery, affordances and perspectives
Green Chemistry ( IF 9.3 ) Pub Date : 2023-04-19 , DOI: 10.1039/d2gc04796a
Marina Cvjetko Bubalo ₁ , Thanos Andreou ₂ , Manuela Panić ₁ , Mia Radović ₁ , Kristina Radošević ₁ , Ivana Radojčić Redovniković ₁

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While exaptation is most impressive when links between very dissimilar contexts are established, it can be even more pervasive when the previously unestablished connection seems surprisingly obvious in retrospect. We herein established such a connection between two major research fields previously advancing in parallel: osmolytes and deep eutectic solvents. Osmolytes are small molecules produced in cells as a response to external stimuli. Based on their individual interaction with macromolecules, single osmolytes are currently categorized as “kosmotropes” (stabilizing proteins) and “chaotropes” (destabilizing them). However, with two or more osmolytes, synergistic effects were also observed on top of cumulative ones. All current attempts to explain these synergistic effects have been studying osmolyte–osmolyte interactions in aqueous solutions, but none has been generally applicable so far, indicating that a new model “beyond kosmotropes and chaotropes” is needed to understand the function of osmolytes. We have gathered enough evidence to formulate a hypothesis of such a new model. First, inspired by patterns frequently observed in nature, five major stabilizing osmolytes (kosmotropes) prominent across kingdoms (trimethylamine N-oxide, sarcosine, glycerophosphorylcholine, dimethylsulfoniopropionate and ectoine) were for the first time employed to form novel two- and three-component DESs with all known natural perturbants/chaotropes (urea, guanidine hydrochloride and arginine). Going beyond the current three-component barrier, we mimicked the exact composition of multi-osmolyte cocktails widely observed in nature and we here report the rapid and consistent formation of deep eutectic systems of unprecedented complexity and the tunable potential of these new systems to stabilize a template protein. Based on these observations, we postulate that, in vivo, osmolytes form deep eutectic systems featuring new, emergent and synergistic properties which govern their interaction with macromolecules. We believe that such bio-inspired, osmolyte-based DESs can be a remarkable new tool to study complex natural systems in higher granularity and to engineer their microenvironment towards efficient and sustainable processes at scale.

中文翻译：

天然多渗透剂鸡尾酒形成了前所未有的复杂性的深层共晶系统：发现、可供性和观点

当非常不同的上下文之间建立联系时，扩展最令人印象深刻，但当以前未建立的联系回想起来似乎非常明显时，它可能会更加普遍。我们在此建立了以前平行推进的两个主要研究领域之间的联系：渗透剂和低共熔溶剂。渗透剂是在细胞中产生的小分子，作为对外部刺激的反应。基于它们与大分子的单独相互作用，单个渗透剂目前被归类为“kosmotropes”（稳定蛋白质）和“chaotropes”（使它们不稳定）。然而，对于两种或多种渗透剂，在累积作用之上还观察到协同效应。目前所有解释这些协同效应的尝试都是在研究水溶液中的渗透剂-渗透剂相互作用，但到目前为止还没有一个普遍适用，这表明需要一种“超越稳液剂和离液剂”的新模型来理解渗透剂的功能。我们已经收集到足够的证据来提出这种新模型的假设。首先，受自然界中经常观察到的模式的启发，五种主要的稳定渗透剂（kosmotropes）在各个王国（三甲胺）中都很突出N-氧化物、肌氨酸、甘油磷酰胆碱、二甲基磺酰基丙酸盐和四氢嘧啶）首次用于与所有已知的天然扰动剂/离液剂（尿素、盐酸胍和精氨酸）形成新型双组分和三组分 DES。超越目前的三组分障碍，我们模拟了自然界中广泛观察到的多渗透剂混合物的确切成分，我们在这里报告了前所未有的复杂性的深度共晶系统的快速和一致的形成，以及这些新系统稳定的可调潜力模板蛋白。基于这些观察，我们假设，在体内，渗透剂形成深共晶系统，具有新的、涌现的和协同的特性，这些特性控制着它们与大分子的相互作用。我们相信，这种受生物启发的、基于渗透剂的 DES 可以成为一种非凡的新工具，可以以更高的粒度研究复杂的自然系统，并将其微环境设计成大规模的高效和可持续过程。

更新日期：2023-04-19

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