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

Alexander Geddes, Caroline E. Paul, Sam Hay, Frank Hollmann, Nigel S. Scrutton

Research output: Contribution to journalArticleScientificpeer-review

25 Citations (Scopus)
22 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)11089-11092
Number of pages4
JournalJournal of the American Chemical Society
Volume138
Issue number35
DOIs
Publication statusPublished - 7 Sep 2016

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