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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 (2019). Emergence of a Negative Activation Heat Capacity during Evolution of a Designed Enzyme. Journal of the American Chemical Society, 141(30):11745-11748.

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, the large reductions in Δ were partially offset by a decrease in Δ and unexpectedly accompanied by a negative activation heat capacity, signaling strong adaptation to the operating temperature. These findings echo reports of temperature-dependent activation parameters for highly evolved natural enzymes and are relevant to explanations of enzymatic catalysis and adaptation to changing thermal environments.

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, the large reductions in Δ were partially offset by a decrease in Δ and unexpectedly accompanied by a negative activation heat capacity, signaling strong adaptation to the operating temperature. These findings echo reports of temperature-dependent activation parameters for highly evolved natural enzymes and are relevant to explanations of enzymatic catalysis and adaptation to changing thermal environments.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Department of Biochemistry
07 Faculty of Science > Department of Biochemistry
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Physical Sciences > Catalysis
Physical Sciences > General Chemistry
Life Sciences > Biochemistry
Physical Sciences > Colloid and Surface Chemistry
Language:English
Date:31 July 2019
Deposited On:25 Sep 2019 13:24
Last Modified:29 Jul 2020 11:22
Publisher:American Chemical Society (ACS)
ISSN:0002-7863
OA Status:Closed
Publisher DOI:https://doi.org/10.1021/jacs.9b02731
PubMed ID:31282667

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