Short peptides assemble to produce enzyme-like catalysts.

Design of a novel catalytic function in proteins and peptides, apart from its inherent practical value, is important for fundamental understanding of enzymatic activity. We will present applications of a minimalistic approach to design of artificial enzymes. We designed a series of short peptides that self-assemble into amyloid-like fibrils to act as Zn²⁺-dependent hydrolases. Zn²⁺ helps stabilize the fibril formation, while also acting as a cofactor to catalyze acyl ester hydrolysis and carbon dioxide hydration. These results indicate that amyloid fibrils are able to not only catalyze their own formation – they also can catalyze chemical reactions. Excitingly, the specific activities shown by these catalytic amyloids are on par with those shown by natural enzymes. Thus, amyloids might have served as intermediates in the evolution of modern-day enzymes. This work has implications for the design of self-assembling nanostructured catalysts including ones containing a variety of biological and non-biological metal ions.

Nature Chem. 2014, 6, 303-309; Proc. Natl. Acad. Sci. U.S.A. 2017, 114, 6191-6196; ACS Cat. 2018, 8, 59-62.