Donor-Acceptor Distance Sampling Enhances the Performance of "better than Nature" Nicotinamide Coenzyme Biomimetics

Journal Article (2016)
Author(s)

Alexander Geddes (The University of Manchester)

CE Paul (TU Delft - BT/Biocatalysis)

Sam Hay (The University of Manchester)

Frank Hollmann (TU Delft - BT/Biocatalysis)

Nigel S. Scrutton (The University of Manchester)

Research Group
BT/Biocatalysis
Copyright
© 2016 Alexander Geddes, C.E. Paul, Sam Hay, F. Hollmann, Nigel S. Scrutton
DOI related publication
https://doi.org/10.1021/jacs.6b05625
More Info
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Publication Year
2016
Language
English
Copyright
© 2016 Alexander Geddes, C.E. Paul, Sam Hay, F. Hollmann, Nigel S. Scrutton
Research Group
BT/Biocatalysis
Issue number
35
Volume number
138
Pages (from-to)
11089-11092
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Abstract

Understanding the mechanisms of enzymatic hydride transfer with nicotinamide coenzyme biomimetics (NCBs) is critical to enhancing the performance of nicotinamide coenzyme-dependent biocatalysts. Here the temperature dependence of kinetic isotope effects (KIEs) for hydride transfer between "better than nature" NCBs and several ene reductase biocatalysts is used to indicate transfer by quantum mechanical tunneling. A strong correlation between rate constants and temperature dependence of the KIE (ΔΔH) for H/D transfer implies that faster reactions with NCBs are associated with enhanced donor-acceptor distance sampling. Our analysis provides the first mechanistic insight into how NCBs can outperform their natural counterparts and emphasizes the need to optimize donor-acceptor distance sampling to obtain high catalytic performance from H-transfer enzymes.