Coordination Funds

可持续和环境友好地生产精细化学品、药品和散装化学品的积木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的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工作，具有良好的选择性、底物范围和催化性能，并且可以从可再生资源中生产。许多酶依赖于无机或有机辅因子，这是一种对进行生物催化反应至关重要的非蛋白质分子。其中一些辅因需要复杂的(再)生成系统。S-腺苷-L-蛋氨酸(SAM，ADOMet)是一种用途最广的辅因子，参与的反应类型非常广泛。山姆在几乎所有的生命形式中都被用作辅基。SAM最突出的功能是作为甲基转移酶(MTS)的甲基供体。然而，硫离子上的所有取代基都参与了各种依赖SAM的酶反应，不同的酶家族使用SAM作为氨丙基和腺苷基团(或自由基)的来源，作为氨基供体，或作为叶立德的来源。这种多功能性使依赖SAM的酶有望成为生物催化的工具。在过去的10年里，人们对使这种辅因子可用于可持续催化和使可获得的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使可持续应用变得触手可及，其中许多进展来自拟议的成员。FOR旨在全面了解依赖SAM的生物催化的全谱，超越甲基转移并利用生理和替代底物。彻底了解依赖SAM的反应、基本机制和控制这些反应的技术是第一个供资阶段的共同目标。建立一个生物催化平台，包括体外和体内系统，以可持续地使用依赖SAM的酶，是第二个预期资助期的主要目标。利用完整的SAM催化化学，这样一个平台将被用来使各种化合物变得容易获得，并创建正交路径。在第一个资助阶段，将研究选定的具有特殊新颖性的酶系统，研究其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合作能力，它们的底物混杂，以及它们作为酶工程支架的适用性。除了将SAM类似物用于表征酶过程和产品多样化外，还将对SAM类似物作为替代代谢途径和体内SAM再生系统组件的有用性进行探索性分析。

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.