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

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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.