The first two authors contributed equally to this work.
Structure-Based Insight into the Asymmetric Bioreduction of the CC Double Bond of α,β-Unsaturated Nitroalkenes by Pentaerythritol Tetranitrate Reductase
Article first published online: 19 NOV 2008
Copyright © 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Advanced Synthesis & Catalysis
Volume 350, Issue 17, pages 2789–2803, November 17, 2008
How to Cite
Toogood, Helen S., Fryszkowska, A., Hare, V., Fisher, K., Roujeinikova, A., Leys, D., Gardiner, John M., Stephens, Gill M. and Scrutton, Nigel S. (2008), Structure-Based Insight into the Asymmetric Bioreduction of the CC Double Bond of α,β-Unsaturated Nitroalkenes by Pentaerythritol Tetranitrate Reductase. Adv. Synth. Catal., 350: 2789–2803. doi: 10.1002/adsc.200800561
- Issue published online: 21 NOV 2008
- Article first published online: 19 NOV 2008
- Manuscript Received: 12 SEP 2008
- UK Biotechnology and Biological Sciences Research Council. Grant Numbers: BBE0107171, BBD0028261
- asymmetric hydrogenation;
- pentaerythritol tetranitrate reductase;
Biocatalytic reduction of α- or β-alkyl-β-arylnitroalkenes provides a convenient and efficient method to prepare chiral substituted nitroalkanes. Pentaerythritol tetranitrate reductase (PETN reductase) from Enterobacter cloacae st. PB2 catalyses the reduction of nitroolefins such as 1-nitrocyclohexene (1) with steady state and rapid reaction kinetics comparable to other old yellow enzyme homologues. Furthermore, it reduces 2-aryl-1-nitropropenes (4a–d) to their equivalent (S)-nitropropanes 9a–d. The enzyme shows a preference for the (Z)-isomer of substrates 4a–d, providing almost pure enantiomeric products 9a–d (ees up to>99%) in quantitative yield, whereas the respective (E)-isomers are reduced with lower enantioselectivity (63–89% ee) and lower product yields. 1-Aryl-2-nitropropenes (5a, b) are also reduced efficiently, but the products (R)-10 have lower optical purities. The structure of the enzyme complex with 1-nitrocyclohexene (1) was determined by X-ray crystallography, revealing two substrate-binding modes, with only one compatible with hydride transfer. Models of nitropropenes 4 and 5 in the active site of PETN reductase predicted that the enantioselectivity of the reaction was dependent on the orientation of binding of the (E)- and (Z)-substrates. This work provides a structural basis for understanding the mechanism of asymmetric bioreduction of nitroalkenes by PETN reductase.