Coiled double amyloid-like fibrils allosterically catalyze hydrolysis of beta-lactam antibiotics

The release of antibiotic compounds into wastewater constitutes a significant and growing health and environmental hazard, particularly contributing to the spread of antibiotic resistant bacterial strains. Here, we demonstrate that amyloid fibrils, consisting of an alternating lysine/phenylalanine -sheet forming short peptide, catalyze hydrolysis of β-lactam antibiotics, the most prominent family of antibiotic compounds, which is further widespread in wastewater. Peptide variant analysis, molecular dynamics (MD) simulations, and cryogenic electron microscopy (cryo-EM) reveal that the β-lactam molecules dock onto the fibrils’ surface via electrostatic interactions with the lysine sidechains. Importantly, catalytic hydrolysis occurs via an allosteric mechanism mediated by a unique coiled double fibril structure in which the anchored β-lactam molecules are embedded within twisted fiber strands, facilitating nucleophilic attacks by the lysine sidechains. Utilization of the catalytic lysine-displaying amyloid fibrils for hydrolytic degradation and removal of β-lactam antibiotics from water was accomplished through display of the fibrils on silica beads placed in a conventional column filtration setup. Amyloid fibrils displaying lysine arrays may furnish a versatile platform for hydrolysis and removal of β-lactam antibiotics in water, underscoring new avenues for addressing the considerable threat of antibiotics water contamination.