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.
Department of Biotechnology, Delft University of Technology , Julianalaan 136, 2628BL Delft, The Netherlands.
J Am Chem Soc. 2016 Sep 7;138(35):11089-92. doi: 10.1021/jacs.6b05625. Epub 2016 Aug 24.
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.
理解烟酰胺辅酶仿生模拟物（NCBs）的酶促氢转移机制对于提高烟酰胺辅酶依赖性生物催化剂的性能至关重要。本文利用“优于天然”NCBs 与几种烯还原酶生物催化剂之间氢转移的动力学同位素效应（KIE）的温度依赖性来指示量子力学隧穿转移。氢/氘转移的速率常数与 KIE（ΔΔH(⧧））的温度依赖性之间存在很强的相关性，这表明与 NCBs 反应更快与增强供体-受体距离采样有关。我们的分析首次深入了解了 NCBs 如何优于其天然对应物，并强调需要优化供体-受体距离采样，以从 H 转移酶获得高催化性能。
