Design of Redox Biocatalysis in Deep Eutectic Solvents (DESiRE)

溶剂的设计和选择特别强调其绿色是目前化学和生物催化的主要焦点。生物催化传统上依赖于水或经典有机介质（主要用于水解酶），或其双相系统。在这方面，深共晶溶剂（DESs）已被确定为“21世纪的溶剂”，并提供了一个新的维度，作为“安全和绿色设计”的生物催化溶剂。简而言之，DESs的资产是基于它们通常的生物起源，以及它们的特性，如熔点低于室温，低挥发性，高热稳定性，类似于离子液体的可调性，可生物降解性，可接受成本的高可用性，以及直接制备。特别是，从各种（生物源）物质设计DESs的高度自由度使得创建可持续的溶剂平台成为可能。DESs在生物催化方面的巨大潜力主要在水解酶（EC3）方面得到了探索，在2008年首次得到应用后。与EC3酶不同，氧化还原酶（EC1）在DESs中很少被大量使用。很少有使用乙醇脱氢酶（ADHs）的例子被记录下来（主要来自我们之前的dfg资助的项目），要么证明使用脱氢酶作为底物进行有机合成，要么了解不同的脱氢酶对氧化还原酶的活性和稳定性的影响。氧化还原生物催化在基于des的应用中仍未得到充分代表，这将由DESiRE的跨学科设置深入解决。总的来说，本文提出的后续项目为阐明蛋白质- des -水相互作用提供了一个明确的策略，这对于理解des中adh的催化作用具有相当大的潜力。特别是实验方法和分子模拟之间的密切合作将在不同的尺度上产生新的见解。此外，该后续项目将进一步为评价其他酶类DESs对酶的催化性能（活性、稳定性和选择性）的影响开辟新的可能性。

Solvent design and selection with a particular emphasis on their greenness is currently a main focus both in chemo- and biocatalysis. Biocatalysis has traditionally relied on either aqueous- or classical organic media (mainly for hydrolases), or biphasic systems thereof. In this respect, Deep Eutectic Solvents (DESs) have been identified as „the solvents of the 21st century“ and offer a new dimension as ‘Safe- and Green-by-Design’ solvents for biocatalysis. In a nutshell, DESs’ assets are based on their often biogenic origin, and their properties such as melting points below room temperature, low volatility, high thermal stability, tuneability analogous to ionic liquids, biodegradability, large availability at acceptable costs, and straightforward preparation. In particular, the high degree of freedom in designing DESs from a variety of (biogenic) substances enables the creation of a sustainable solvent platform. The enormous potential of DESs for biocatalytic applications has been mainly explored for hydrolases (EC3), after their first application demonstrated in 2008. Different then EC3 enzymes, oxidoreductases (EC1) have only rarely been employed in DESs at predominant amounts. Few examples for the use of alcohol dehydrogenases (ADHs) have been documented (mainly from our previous DFG-funded project) either to demonstrate the use of DESs for organic synthesis while using a DES component as substrate or to understand the effect of different DESs on the activity and stability of a redox enzyme. Redox biocatalysis is still underrepresented for DES-based applications which will be addressed deeply by the interdisciplinary setup of DESiRE. Overall, the here presented follow-up project represents a clear strategy to elucidate the protein-DES-water interactions, which possess a considerable potential for understanding the ADH-catalysis in DESs. Especially the close collaboration between experimental methods and molecular simulations will lead to new insights on different scales. Moreover, this follow-up project will further open new possibilities to evaluate other enzyme classes for the effects of DESs on catalytic performance (activity, stability and selectivity) of enzymes.