Emergence of a Negative Activation Heat Capacity during Evolution of a Designed Enzyme

Bunzel, H Adrian; Kries, Hajo; Marchetti, Luca; Zeymer, Cathleen; Mittl, Peer R E; Mulholland, Adrian J; Hilvert, Donald

doi:10.1021/jacs.9b02731

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Bunzel, H. A., Kries, H., Marchetti, L., Zeymer, C., Mittl, P. R. E., Mulholland, A. J., & Hilvert, D. (2019). Emergence of a Negative Activation Heat Capacity during Evolution of a Designed Enzyme. Journal of the American Chemical Society, 141(30), 11745–11748. https://doi.org/10.1021/jacs.9b02731

Abstract

Temperature influences the reaction kinetics and evolvability of all enzymes. To understand how evolution shapes the thermodynamic drivers of catalysis, we optimized the modest activity of a computationally designed enzyme for an elementary proton-transfer reaction by nearly 4 orders of magnitude over 9 rounds of mutagenesis and screening. As theorized for primordial enzymes, the catalytic effects of the original design were almost entirely enthalpic in origin, as were the rate enhancements achieved by laboratory evolution. However, t