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    Item type:Project, Access status: without files ,
    Design of Redox Biocatalysis in Deep Eutectic Solvents
    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.
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    Entwicklung und experimentelle Validierung einer molekulardynamischen Simulationsmethode zur Vorausberechnung von Adsorptionsisothermen von Proteinen
    Die Produktion von Proteinen als Biopharmazeutika ist ein wichtiger und wachsender Zweig der pharmazeutischen Industrie. Gemäß dem Stand der Technik erfolgt dabei die Aufreinigung der Produkte mittels verschiedener chromatographischer Methoden. Deren Entwicklung basiert für die jeweiligen Produkte auf umfangreichen und aufwendigen experimentellen Arbeiten.In diesem Projekt sollen experimentelle Methoden und molekulardynamische (MD) Simulationen in enger Verknüpfung eingesetzt werden um die Ionenaustauschadsorption von Proteinen zu beschreiben. Experimentell erfolgen eine umfangreiche Charakterisierung vorhandener Adsorbentien und die Beschreibung der vorliegenden Adsorptionseigenschaften. Parallel dazu werden MD-Simulationen der Adsorption durchgeführt und die beschreibenden Parameter der Proteinadsorption am Beispiel des SMA-Modells bestimmt. Dies bietet die Grundlage um anschließend eine optimierte Adsorbensstruktur zu beschreiben.Im Rahmen dieses Forschungsprojekts werden MD Methoden erfolgreich angewendet um die Ionenaustauschadsorption von Proteinen zu beschreiben. Dafür wird ein validiertes Modell zur vollständigen Beschreibung einer Adsorptionsisotherme bei verschiedenen Prozessparametern entwickelt. Dies ermöglicht erstmalig in silico die vollständige Vorhersage der Adsorptionsisothermen von Proteinen. Weiterhin sind die einzelnen Wechselwirkungszentren an den Modellproteinen charakterisiert, so dass auf dieser Basis neue Adsorbentien beschrieben sind, welche verbesserte Adsorptionseigenschaften aufweisen.Nach erfolgreichem Abschluss dieses Projekts ergibt sich die Möglichkeit die erarbeitete Methode auf beliebige Systeme zu übertragen um zukünftig mit geringerem Aufwand die chromatographischen Methoden zur Aufreinigung von pharmazeutisch relevanten Proteinen zu entwickeln.
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    Rational Analysis of Structural and Functional Changes of Oxidoreductases in Non-Conventional Reaction Media
    Establishing biotransformation in non-aqueous media is recognised as a hot-topic in the biocatalysis community owing to several advantages: high-solubility of synthetically interesting hydrophobic substrates, reduced risk for water-induced protein denaturation, andelimination of undesired side reactions. Whereas a high number of research studies on the application of hydrolases (EC3) in low-water media are published, very few publications are available on the use of oxidoreductases (EC1) in this non-conventional environment. This isunfortunate as oxidoreductases catalyses synthesis of valuable chemical compounds which are of high interest for pharma and agro, but as well as for bulk chemical industries. Among the oxidoreductase enzymes, alcohol dehydrogenases (ADHs) are predominantly appliedin organic synthesis not only at laboratory but also at industrial scale. However, these applications are mainly based on the use of aqueous media. Due to the lack of an understanding for the effects of organic solvents, which would replace the water as the reaction environment,in the present project proposal we focus on a rigorous evaluation of these effects on the ADH-catalysis. For this purpose, two model ADHs will be characterized in commonly used organic solvents (e.g. Ethyl acetate and methyl tert-butyl ether), in greener ones (e.g. 2-methyltetrahydrofuran and cyclopentyl methyl ether) as well as in deep-eutectic-solvents, which are a new generation of solvents with more sustainable characteristics compared to some ionic liquids. Thereby, the focus will be on relating solvent properties (e.g. hydrophobicity, molecular structure, and water content) to ADH catalysis characteristics (e.g. activity, stability, and selectivity). Molecular dynamics simulations will be performed for a deepunderstanding of the interactions between the protein, solvents, and water. Having elucidated and understood the effects of the organic solvent properties on the enzyme catalysis, our final goal is to develop general solvent selection rules taking into account the solventproperties. Overall, the here presented project topic has not been investigated yet and it represents a clear strategy to elucidate the protein-solvent-water interactions, which possess a considerable potential for understanding the ADH-catalysis in non-aqueous media.Especially the close collaboration between experimental methods and molecular simulations will lead to new insights on different scales. Moreover, this research project will open new possibilities to evaluate other enzyme classes for the effects of organic solvents on Enzyme characteristics.
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