DataSheet1_An artificial self-assembling peptide with carboxylesterase activity and substrate specificity restricted to short-chain acid p-nitrophenyl esters.docx

Natural enzymes possess remarkable catalytic activity and high substrate specificity. Many efforts have been dedicated to construct artificial enzymes with high catalytic activity. However, how to mimic the exquisite substrate specificity of a natural enzyme remains challenging because of the complexity of the enzyme structure. Here, we report artificial carboxylesterases that are specific for short chain fatty acids and were constructed via peptide self-assembly. These artificial systems have esterase-like activity rather than lipase-like activity towards p-nitrophenyl esters. The designer peptides self-assembled into nanofibers with strong β-sheet character. The extending histidine units and the hydrophobic edge of the fibrillar structure collectively form the active center of the artificial esterase. These artificial esterases show substrate specificity for short-chain acids esters. Moreover, 1-isopropoxy-4-nitrobenzene could function as a competitive inhibitor of hydrolysis of p-nitrophenyl acetate for an artificial esterase.

天然酶展现出卓越的催化活性和高底物特异性。众多研究致力于构建具有高催化活性的人工酶。然而，由于酶结构的复杂性，如何模拟天然酶的精细底物特异性依然是一项挑战。在本研究中，我们报道了一种针对短链脂肪酸的人工羧酸酯酶，该酶通过肽自组装构建而成。这些人工系统对对硝基苯甲酸酯表现出酯酶类而非脂肪酶类的活性。设计肽自组装成具有强烈β-折叠特性的纳米纤维。延伸的组氨酸单元和纤维状结构的疏水边缘共同构成了人工酯酶的活性中心。这些人工酯酶对短链酸酯表现出底物特异性。此外，1-异丙氧基-4-硝基苯可作为人工酯酶水解对硝基苯甲酸乙酯的竞争性抑制剂。