Overcoming limitations of L-threonine aldolases in biocatalysis: Highly efficient applications via reaction engineering

克服 L-苏氨酸醛缩酶在生物催化中的局限性：通过反应工程实现高效应用

• 批准号: 454753456
• 负责人: Professor Dr. Harald Gröger
• 金额: --
• 依托单位: Institut für Technische Biokatalyse V-6
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/454753456?language=en
• 关键词: Overcoming; limitations; threonine; aldolases; biocatalysis

In this interdisciplinary tandem project by the working groups Liese (Bioprocess Engineering) and Gröger (Industrial Organic Synthesis), the aim is to generate a basic scientific understanding of efficient diastereoselective synthesis processes using L-threonine aldolases. These enzymes catalyze asymmetric aldol reactions to form α-amino β-hydroxy carboxylic acids. Currently, the major disadvantage of this enzymatic reaction type is the unfavorable thermodynamic equilibrium, which leads to unwanted diastereomeric ratios of the products. Starting from a model reaction, a fundamental understanding of the competing thermodynamic and kinetic control of the biocatalytic reaction system will be developed. The establishment of inline (NMR) and offline (HPLC) analytical methods will allow a comprehensive kinetic and thermodynamic characterization depending on the reaction progress. Based on this, reaction and enzyme measures to overcome the thermodynamic and kinetic limitations are evaluated and implemented in a continuously operated reactor. At the end of this project, this comprehensive study should demonstrate that aldol reactions catalyzed by L-threonine aldolases are a worthy alternative to conventional chemical synthesis processes for the synthesis of alpha-amino beta-hydroxy carboxylic acids.

在Liese（生物工艺工程）和Gröger（工业有机合成）工作组的跨学科串联项目中，目的是对使用L-苏氨酸醛缩酶的有效非对映选择性合成过程产生基本的科学理解。这些酶催化不对称羟醛缩合反应形成α-氨基β-羟基羧酸。目前，这种酶促反应类型的主要缺点是不利的热力学平衡，这导致产物的不希望的非对映异构体比率。从一个模型反应，竞争的生物催化反应系统的热力学和动力学控制的基本理解将被开发。在线（NMR）和离线（HPLC）分析方法的建立将允许根据反应进程进行全面的动力学和热力学表征。在此基础上，反应和酶的措施，以克服热力学和动力学的限制进行评估，并在连续操作的反应器中实施。在这个项目的最后，这项全面的研究应该证明，由L-苏氨酸醛缩酶催化的羟醛缩合反应是一个有价值的替代传统的化学合成方法的α-氨基β-羟基羧酸的合成。