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Data from: Random heteropolymers as enzyme mimics

Yu, Hao1; Eres, Marco1; Hilburg, Shayna2; Kang, Philjun1; Jin, Tianyi2; Grigoropoulos, Alexandra1; Li, Zhixia3; Loh, Daniel1; Jayapurna, Ivan1; Ruan, Zhiyuan1; Fu, Wen4; Yang, Feipeng5; Ganesh, Priya2; Toste, Kali1; Li, Shuni1; Guo, Jinghua5; Huang, Haiyan1; Toste, Dean1; Britt, David4; Z, Y36; Alexander-Katz, Alfredo2; Xu, Ting15

Published Jul 10, 2026 on Dryad. https://doi.org/10.5061/dryad.ghx3ffc2r

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Abstract

Despite successes in replicating the primary–secondary–tertiary structure hierarchy of protein, it remains unknown to synthetically materialize protein functions that are deeply rooted in their chemical, structural and dynamic heterogeneities. We propose that for polymers with backbone chemistries different from that of proteins, programming spatial and temporal projections of sidechains at the segmental level can be effective in replicating protein behaviours; and leveraging the rotational freedom of polymer can mitigate deficiencies in monomeric sequence specificity and achieve behaviour uniformity at the ensemble level. Here, guided by the active site analysis of about 1,300 metalloproteins, we design random heteropolymers (RHPs) as enzyme mimics based on one-pot synthesis. We introduce key monomers as the equivalents of the functional residues of protein and statistically modulate the chemical characteristics of key monomer-containing segments, such as segmental hydrophobicity. The resultant RHPs form pseudo-active sites that provide key monomers with protein-like microenvironments, co-localize substrates with catalytic or cofactor-binding sidechains and catalyse reactions such as oxidation and cyclization of citronellal with isopulegol/menthoglycol selectivity. This RHP design led to enzyme-like materials that can retain catalytic activity under non-biological conditions, are compatible with scalable processing and have expanded substrate scope, including environmentally long-lasting antibiotic tetracycline.