Natural oxidases (eg, glucose oxidase, and laccase) mainly rely on cofactors and well-arranged amino acid residues for catalyzing electron-transfer reactions. However, the unfolding of proteins, caused by acidification or heating, can induce irreversible inactivation of the enzymes. 

Enzyme-inspired supramolecular catalysts hold promise in cofactor-free catalysis. Such catalysts may help to resolve the mechanisms by which simple molecules evolved into cofactor-dependent enzymes. 

Recently, a research team led by Prof. DING Baoquan from the National Center for Nanoscience and Technology (NCNST) of the Chinese Academy of Sciences and Prof. WANG Zhengang from Beijing University of Chemical Technology demonstrated a novel strategy for the construction of cofactor-free oxidase-mimetic nanomaterials from self-assembled histidine-rich peptides. The study was published in Nature Materials. 

Prof. DING has been working in the field of biomolecule-based multifunctional nanostructures. His group has constructed various cofactor-containing catalytical biomaterials via the self-assembly of DNA, peptide and polysaccharide. However, it remains unknown whether residues at the active site can catalyze similar chemical reactions in the absence of the cofactor. 

In this study, the described cofactor-free, non-conjugated supramolecular catalyst exhibits redox activity that was dependent on the cooperation between neighboring functional groups.  

The researchers assembled oligohistidine peptides into ordered nanostructures that exhibit activity in H₂O₂ reduction and substrate (TMB, HVA or NADH) oxidization. The activity of the catalyst can be recovered after ten or more cycles of thermal or acid treatment, making them more robust than haemin-containing complexes.  

Furthermore, the activity of the catalyst was enhanced by increasing the catalytic surface area. The conjugation of a fibril-forming inert peptide with the oligohistidine led to the formation of nanoscale fibrils and increased the turnover frequency by almost one order of magnitude. 

This study designed cofactor-free oxidase-mimicking catalysts, and proposed a novel mechanism for catalyzed electron-transfer reactions.  

The cofactor-free supramolecular catalysts provide a putative model for primitive enzymes, and their environmental-induced deactivation and activation could explain how these supramolecular peptide assemblies would survive under prebiotic conditions.