Coordination Funds

协调基金

• 批准号: 530630666
• 负责人: Professorin Dr. Jennifer Andexer
• 金额: --
• 依托单位: Institut für Pharmazeutische Wissenschaften
• 依托单位国家: 德国
• 项目类别: Research Units
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/530630666?language=en
• 关键词: Coordination; Funds

The sustainable and environmentally friendly production of building blocks for fine chemicals, pharmaceuticals, and bulk chemicals is an urgent and important task and requires a re-thinking of current established views. Biocatalytic systems using renewable and sustainable feedstocks and energy sources will be key components to achieve this goal, as enzymes operate at physiological temperatures, have favourable selectivity, substrate range, and catalytic properties, and can be produced from renewable sources. Many enzymes are dependent on an inorganic or organic cofactor, a non-protein molecule that is crucial for carrying out the biocatalytic reaction. Some of these cofactors require complex (re)generation systems. S-adenosyl-L-methionine (SAM, AdoMet) is one of the most versatile cofactors and is involved in a remarkably wide range of reaction types. SAM is used as a cosubstrate in almost all life forms. The most prominent function of SAM is to serve as a methyl group donor for methyltransferases (MTs). However, all substituents at the sulfonium ion are involved in various SAM-dependent enzymatic reactions, and different enzyme families use SAM as a source of aminopropyl- and adenosyl groups (or radicals), as amino donor, or as a source of ylides. This versatility makes SAM-dependent enzymes promising tools for biocatalysis. Over the past 10 years, interest in making this cofactor accessible for sustainable catalysis and diversify the accessible products has steadily increased. Recent advances in the fields of regeneration systems and cofactor analogues, many of which originated from members of the proposed FOR, bring sustainable application within reach. The FOR aims to gain a comprehensive understanding of the full spectrum of SAM-dependent biocatalysis, extending beyond methyl transfer and utilizing physiological and alternative substrates. A thorough understanding of SAM-dependent reactions, the underlying mechanisms, and the techniques to control them are the shared objectives of the first funding period. Establishing a biocatalytic platform including in vitro and in vivo systems for the sustainable use of SAM-dependent enzymes is the main objective of a second anticipated funding period. Using the complete range of SAM-catalyzed chemistry, such a platform will be used to make a wide variety of compounds accessible and to create orthogonal pathways. In the first funding phase, selected enzyme systems of particular novelty will be studied with respect to their catalytic mechanisms and their function in biological systems. We will investigate their ability to cooperate in multienzyme reactions, their substrate promiscuity, and their suitability as scaffolds for enzyme engineering. An exploratory analysis of SAM analogues' usefulness as components in alternative metabolic pathways and in vivo SAM regeneration systems will be conducted in addition to employing them for the characterisation of enzyme processes and product diversification.

精细化学品、药品和大宗化学品原料的可持续和环保生产是一项紧迫而重要的任务，需要重新思考当前的既定观点。使用可再生和可持续原料和能源的生物催化系统将是实现这一目标的关键组成部分，因为酶在生理温度下运行，具有良好的选择性、底物范围和催化特性，并且可以由可再生来源生产。许多酶依赖于无机或有机辅因子，这是一种对于进行生物催化反应至关重要的非蛋白质分子。其中一些辅助因子需要复杂的（重新）生成系统。 S-腺苷-L-甲硫氨酸（SAM，AdoMet）是最通用的辅助因子之一，参与非常广泛的反应类型。 SAM 被用作几乎所有生命形式的共底物。 SAM 最突出的功能是充当甲基转移酶 (MT) 的甲基供体。然而，锍离子上的所有取代基都参与各种 SAM 依赖性酶促反应，并且不同的酶家族使用 SAM 作为氨丙基和腺苷基（或自由基）的来源、氨基供体或叶立德的来源。这种多功能性使得 SAM 依赖性酶成为生物催化的有前途的工具。在过去的 10 年里，人们对将这种辅助因子用于可持续催化以及使可用产品多样化的兴趣稳步增加。再生系统和辅因子类似物领域的最新进展（其中许多源自拟议的 FOR 成员）使可持续应用变得触手可及。 FOR 旨在全面了解 SAM 依赖性生物催化的全谱，超越甲基转移并利用生理和替代底物。彻底了解 SAM 依赖性反应、基本机制以及控制它们的技术是第一个资助期的共同目标。第二个预期资助期的主要目标是建立一个生物催化平台，包括体外和体内系统，以可持续利用 SAM 依赖性酶。利用完整的 SAM 催化化学，这样的平台将用于制备多种化合物并创建正交途径。在第一个资助阶段，将研究选定的具有特别新颖性的酶系统的催化机制及其在生物系统中的功能。我们将研究它们在多酶反应中的协作能力、底物混杂性以及它们作为酶工程支架的适用性。除了利用 SAM 类似物表征酶过程和产品多样化之外，还将对 SAM 类似物作为替代代谢途径和体内 SAM 再生系统的成分的用途进行探索性分析。