The complex, three-dimensional structures that enzymes maintain to exhibit catalytic activity often denature in non-biological environments. Model peptides, which mimic enzyme active sites through self-assembly, offer a route to control the placement of chemistry through robust backbone structures. Mimics that utilize amyloid structures in particular are promising as the amyloid backbone demonstrates high resistance to thermal and chemical degradation. However, the full extent of their stability and underlying mechanism has yet to be realized. Here, we set out to define the activity of catalytic amyloids in extreme environments by combining catalytic activity assays with non-linear 2D vibrational spectroscopy (2DIR) techniques that are sensitive to backbone hydrogen bonding. We found that these materials maintain activity beyond 120 °C and experience a 30-fold increase in catalytic efficiency at their optimum temperature of 81 °C. In a deviation from typical Arrhenius behavior, the decrease in activity above the optimum temperature is not correlated with backbone denaturation. Instead, <i>in situ</i> 2DIR reveals subtle backbone hydrogen bond organization into amyloid-like structures of greater thermal stability. The same structure is observed in organic solvents, where catalytic amyloids maintain hydrolysis activity in co-solvents of varying polarity. These findings are supported with molecular modeling, which shows that shorter, less competitive bonding lifetimes with co-solvents further stabilizes self-associative backbone interactions. We demonstrate that catalytic amyloids survive extreme reaction environments through structural reinforcement mechanisms to maintain their enzyme-like functions. This work highlights new advantages in utilizing the amyloid backbone when designing enzyme mimics.

Structural adaptation of catalytic amyloid materials to extreme environments

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