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

在这个由Liese（生物过程工程）和Gröger（工业有机合成）工作组进行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位选择性合成过程产生基本的科学理解。这些酶催化不对称醛醇反应生成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，这导致产物的非对映异构体比例。从模型反应开始，对生物催化反应系统的竞争热力学和动力学控制的基本理解将得到发展。建立在线（NMR）和离线（HPLC）分析方法将允许根据反应过程进行全面的动力学和热力学表征。在此基础上，对克服热力学和动力学限制的反应和酶措施进行了评估，并在连续运行的反应器中进行了实施。在本项目结束时，这项综合研究将证明l -苏氨酸醛缩酶催化的醛醇反应是一种有价值的替代传统化学合成工艺合成α -氨基-羟基羧酸的方法。

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.