biostudies-literatureYuan YNational Natural Science Foundation of ChinaNational Natural Science Foundation of China (National Science Foundation of China)5636https://www.ebi.ac.uk/biostudies/studies/S-EPMC11224359biostudies-literatureUnknown15(1)Natural antimicrobial peptides (AMPs) and enzymes (AMEs) are promising non-antibiotic candidates against antimicrobial resistance but suffer from low efficiency and poor stability. Here, we develop peptide nanozymes which mimic the mode of action of AMPs and AMEs through de novo design and peptide assembly. Through modelling a minimal building block of IHIHICI is proposed by combining critical amino acids in AMPs and AMEs and hydrophobic isoleucine to conduct assembly. Experimental validations reveal that IHIHICI assemble into helical β-sheet nanotubes with acetate modulation and perform phospholipase C-like and peroxidase-like activities with Ni coordination, demonstrating high thermostability and resistance to enzymatic degradation. The assembled nanotubes demonstrate cascade antifungal Nature communicationsStable peptide-assembled nanozyme mimicking dual antifungal actions.PMC112243598193005022121003Jiang JKong LYu LHe JWang CChen LFu ZWang HYan XSong KSun MLiu YWang QWang RZhang XGao LJiang BCheng MWang XCui CFang LYuan YfalseStable peptide-assembled nanozyme mimicking dual antifungal actions.Natural antimicrobial peptides (AMPs) and enzymes (AMEs) are promising non-antibiotic candidates against antimicrobial resistance but suffer from low efficiency and poor stability. Here, we develop peptide nanozymes which mimic the mode of action of AMPs and AMEs through de novo design and peptide assembly. Through modelling a minimal building block of IHIHICI is proposed by combining critical amino acids in AMPs and AMEs and hydrophobic isoleucine to conduct assembly. Experimental validations reveal that IHIHICI assemble into helical β-sheet nanotubes with acetate modulation and perform phospholipase C-like and peroxidase-like activities with Ni coordination, demonstrating high thermostability and resistance to enzymatic degradation. The assembled nanotubes demonstrate cascade antifungal 2024-01-01T00:00:00Z2024 Jul2025-04-04T19:23:06.799Z2025-04-04T19:23:06.799ZS-EPMC112243593896523210.1038/s41467-024-50094-6