Zhang Ningning, Wu Changzhu
Institute of Microbiology, Technische Universität Dresden, Zellescher Weg 20b, 01217 Dresden, Germany.
Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230 Odense, Denmark.
ACS Synth Biol. 2022 Nov 18;11(11):3797-3804. doi: 10.1021/acssynbio.2c00387. Epub 2022 Nov 7.
Artificial enzymes are becoming a powerful toolbox for selective organic syntheses. Herein, we first propose an advanced artificial enzyme by polymeric modularity as an efficient aldolase mimic for aqueous asymmetric aldol reactions. Based on an in-depth understanding of the aldolase reaction mechanism and our previous work, we demonstrate the modular design of protein-polymer conjugates by co-incorporating l-proline and styrene onto a noncatalytic protein scaffold with a high degree of controllability. The tailored conjugates exhibited remarkable catalytic performance toward the aqueous asymmetric aldol reaction of -nitrobenzaldehyde and cyclohexanone, achieving 94% conversion and excellent selectivity (95/5 diastereoselectivity, 98% enantiomeric excess). In addition, this artificial enzyme showed high tolerance against extreme conditions (e.g., wide pH range, high temperature) and could be reused for more than four times without significant loss of reactivity. Experiments have shown that the artificial enzyme displayed broad specificity for various aldehydes.
人工酶正成为选择性有机合成的一个强大工具库。在此，我们首次通过聚合物模块化提出一种先进的人工酶，作为用于水相不对称羟醛反应的高效醛缩酶模拟物。基于对醛缩酶反应机制的深入理解以及我们之前的工作，我们通过将L-脯氨酸和苯乙烯共同掺入具有高度可控性的非催化蛋白质支架上，展示了蛋白质-聚合物缀合物的模块化设计。定制的缀合物对硝基苯甲醛和环己酮的水相不对称羟醛反应表现出显著的催化性能，实现了94%的转化率和优异的选择性（95/5非对映选择性，98%对映体过量）。此外，这种人工酶对极端条件（如宽pH范围、高温）表现出高耐受性，并且可以重复使用四次以上而不会显著损失反应活性。实验表明，该人工酶对各种醛具有广泛的特异性。
