A supramolecular metalloenzyme possessing robust oxidase-mimetic catalytic function

• Published in: Nature communications 2023-07, Vol.14 (1), p.4040-4040, Article 4040
• Main Authors: Xu, Shichao, Wu, Haifeng, Liu, Siyuan, Du, Peidong, Wang, Hui, Yang, Haijun, Xu, Wenjie, Chen, Shuangming, Song, Li, Li, Jikun, Shi, Xinghua, Wang, Zhen-Gang
• Format: Article
• Language: English
• Subjects: 140/131; 147/143; 147/3; 639/638/541/966; 639/638/77; Amino acid sequence; Amino acids; Aqueous environments; Biomimetics; Catalysts; Catechol; Catechol oxidase; Clusters; Copper; Environmental changes; Enzymes; Functional groups; Humanities and Social Sciences; multidisciplinary; Nucleotides; Oxidase; Science; Science (multidisciplinary); Self-assembly; Synthesis
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-39779-6

Enzymes fold into unique three-dimensional structures to distribute their reactive amino acid residues, but environmental changes can disrupt their essential folding and lead to irreversible activity loss. The de novo synthesis of enzyme-like active sites is challenging due to the difficulty of replicating the spatial arrangement of functional groups. Here, we present a supramolecular mimetic enzyme formed by self-assembling nucleotides with fluorenylmethyloxycarbonyl (Fmoc)-modified amino acids and copper. This catalyst exhibits catalytic functions akin those of copper cluster-dependent oxidases, and catalytic performance surpasses to date-reported artificial complexes. Our experimental and theoretical results reveal the crucial role of periodic arrangement of amino acid components, enabled by fluorenyl stacking, in forming oxidase-mimetic copper clusters. Nucleotides provide coordination atoms that enhance copper activity by facilitating the formation of a copper-peroxide intermediate. The catalyst shows thermophilic behavior, remaining active up to 95 °C in an aqueous environment. These findings may aid the design of advanced biomimetic catalysts and offer insights into primordial redox enzymes. The de novo synthesis of enzyme-like active sites remains a challenge, due to the difficulties in imitating the spatial arrangement of the functional groups. Here, the authors report the construction of a supramolecular mimetic enzyme possessing catechol oxidase-like copper-cluster active sites.