Random heteropolymers as enzyme mimics
Article Date = 31 December 2025
Article URL = https://www.nature.com/articles/s41586-025-09860-9
Article Title = Random heteropolymers as enzyme mimics
Article Image =
Summary
This Nature paper demonstrates that synthetic random heteropolymers (RHPs) can act as enzyme mimics. The authors show RHPs that bind haem and create catalytic microenvironments capable of enzyme-like chemistry, including peroxidase-like reactivity and catalysing citronellal cyclisation. The work combines synthesis and characterisation of RHP variants (RHP-P1, RHP-S1, RHP-H1, etc.), kinetic studies, spectroscopies (NMR, EPR, XANES), small-angle neutron scattering, size-exclusion chromatography, and all-atom molecular dynamics to link sequence-level heterogeneity and chain dynamics to functional outcomes.
The key messages are that relatively unstructured, sequence-random polymers can (1) consistently bind cofactors such as haem across polymer chains, (2) form local hydrophobic/hydrophilic patterns that create catalytic pockets, and (3) perform useful catalytic transformations. The paper includes sequence simulation tools and raw data links for reproducibility, and the authors note a PCT patent filing for some inventions reported.
Key Points
- Random heteropolymers (RHPs) can bind haem cofactors and display enzyme-like catalytic activity despite sequence heterogeneity.
- Heme-bound RHPs (e.g. RHP-H1) show consistent heme association across the polymer population (SEC and spectroscopy evidence).
- Molecular dynamics and PCA analyses reveal heterogeneous chain dynamics and localised surface compositions that mimic enzyme microenvironments.
- RHPs catalyse reactions such as citronellal cyclisation and peroxidase-type chemistry; kinetic and spectroscopic data support functional performance.
- Small-angle neutron scattering, NMR, EPR and XANES provide complementary structural and electronic information tying structure to activity.
- Sequence simulation and code repositories (RHPapp and related tools) and raw data are provided to support reproducibility.
- The work suggests a route to designer synthetic catalysts that do not require precise folding like proteins, widening practical options for biomimetic catalysis.
Why should I read this?
Short version: if you care about new ways to make catalysts that behave like enzymes without the headache of protein design, this is worth a skim — and probably a deeper read. The paper shows synthetic polymers can create useful catalytic pockets and work with haem cofactors, backed by solid experimental and simulation evidence. It’s a neat shortcut towards robust, tuneable catalysts for chemistry and environmental applications.
Author style
Punchy: this is a high-impact demonstration that ‘random’ doesn’t mean ‘useless’. The results are relevant if you’re into catalysis, polymer design or applied biomimetics — the paper saves you time by proving function can arise from sequence diversity rather than painstaking sequence control.