Scientists Design Cofactor-free oxidase-mimetic Nanomaterials from Self-assembled Histidine-rich Peptides

Data:2020-11-30  |  【 A  A  A 】  |  【Print】 【Close

Natural oxidases (eg, glucose oxidase, laccase, etc.) 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 lead us to resolve the mechanisms by which simple molecules evolved into cofactor-dependent enzymes.

Prof. DING Baoquan from the National Center for Nanoscience and Technology (NCNST) has been working in the field of biomolecule-based multifunctional nanostructures (Angew. Chem. Int. Ed., 2018, 57, 15486; Nature Biotechnol., 2018, 3, 258; Nature Mater., 2020, DOI: 10.1038/s41563-020-0793-6). They constructed various cofactor-containing catalytical biomaterials via the self-assembly of DNA, peptide and polysaccharide (Chem. Eur. J. 2019, 25, 12576; ACS Catal. 2018, 8, 7016; ACS Nano 2017, 11, 7251). However, it remains unknown whether residues at the active site can catalyze similar chemical reactions in the absence of the cofactor.

Recently, a research team led by Prof. DING and Prof. WANG Zhen-gang from Beijing University of Chemical Technology (BUCT) 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.

In this work, they described a cofactor-free, non-conjugated supramolecular catalyst exhibiting redox activity that was dependent on the cooperation between neighboring functional groups. They 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 is 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.

Herein, scientists design cofactor-free oxidase-mimicking catalysts. Meanwhile, they propose 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.

The research was supported by the National Natural Science Foundation of China, the Fundamental Research Funds for the Central Universities, the Science Fund for Creative Research Groups of the National Natural Science Foundation of China, the National Basic Research Programs of China, the National Natural Science Foundation of Beijing, the Beijing Municipal Science and Technology Commission, the Key Research Program of Frontier Sciences, the Strategic Priority Research Program of the Chinese Academy of Sciences and the K. C. Wong Education Foundation.


Fig.1 a) Structures of horseradish peroxidase and sperm whale myoglobin ; b) Schematic illustration showing the self-assembly of the designed peptides into β-sheets and planar crystal nanomaterials; c) Working model of periodically arranged peptide chains and side-chain groups for catalysis.


Fig.2 a) SEM image, SAED pattern and HRTEM image of the H15-based self-assembled nanostructures; b) Effect of peptide length on CD intensity and maximum absorbance wavelength (left) and the length-dependent activity at different peptide concentrations (right); c) Proposed transformation process; d) Thermal and pH response of the catalytic activity in H2O2 oxidation of TMB for H15 peptides and HRP.




DING Bao-Quan

National Center for Nanoscience and Technology (NCNST)

E-mail: dingbq 







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