title: Donor-Acceptor Distance Sampling Enhances the Performance of "Better than Nature" Nicotinamide Coenzyme Biomimetics.
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.
authors.affiliation: BBSRC/EPSRC Centre for Synthetic Biology of Fine and Speciality Chemicals (SYNBIOCHEM), Manchester Institute of Biotechnology and School of Chemistry, The University of Manchester , 131 Princess Street, Manchester M1 7DN, United Kingdom.
authors.forename: Alexander
authors.initials: A
authors.lastname: Geddes
authors.affiliation: Department of Biotechnology, Delft University of Technology , Julianalaan 136, 2628BL Delft, The Netherlands.
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Paul
authors.affiliation: BBSRC/EPSRC Centre for Synthetic Biology of Fine and Speciality Chemicals (SYNBIOCHEM), Manchester Institute of Biotechnology and School of Chemistry, The University of Manchester , 131 Princess Street, Manchester M1 7DN, United Kingdom.
authors.forename: Sam
authors.initials: S
authors.lastname: Hay
authors.affiliation: Department of Biotechnology, Delft University of Technology , Julianalaan 136, 2628BL Delft, The Netherlands.
authors.forename: Frank
authors.initials: F
authors.lastname: Hollmann
authors.affiliation: BBSRC/EPSRC Centre for Synthetic Biology of Fine and Speciality Chemicals (SYNBIOCHEM), Manchester Institute of Biotechnology and School of Chemistry, The University of Manchester , 131 Princess Street, Manchester M1 7DN, United Kingdom.
authors.forename: Nigel S
authors.initials: NS
authors.lastname: Scrutton
mesh_terms: D055162:Biocatalysis; D040761:Biomimetic Materials / Q000737:chemistry*; D003067:Coenzymes / Q000378:metabolism*; D007700:Kinetics; D009536:Niacinamide / Q000378:metabolism*; D013696:Temperature
chemical_list: D003067:Coenzymes; D009536:Niacinamide