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Structure-Based Insight into the Asymmetric Bioreduction of the C=C Double Bond of α,β-Unsaturated Nitroalkenes by Pentaerythritol Tetranitrate Reductase

Authors
  • Toogood, Helen S.1
  • Fryszkowska, Anna2
  • Hare, Victoria1
  • Fisher, Karl3
  • Roujeinikova, Anna1
  • Leys, David1
  • Gardiner, John M.2
  • Stephens, Gill M.3
  • Scrutton, Nigel S.1
  • 1 Manchester Interdisciplinary Biocentre, Faculty of Life Sciences, University of Manchester, 131 Princess Street, Manchester M1 7DN, U.K.
  • 2 Manchester Interdisciplinary Biocentre, Department of Chemistry, University of Manchester, 131 Princess Street, Manchester M1 7DN, U.K.
  • 3 Manchester Interdisciplinary Biocentre, School of Chemical Engineering and Analytical Sciences, University of Manchester, 131 Princess Street, Manchester M1 7DN, U.K.
Type
Published Article
Journal
Advanced Synthesis & Catalysis
Publisher
Wiley (John Wiley & Sons)
Publication Date
Nov 17, 2008
Volume
350
Issue
17
Pages
2789–2803
Identifiers
DOI: 10.1002/adsc.200800561
PMID: 20396603
PMCID: PMC2854801
Source
PubMed Central
Keywords
License
Unknown
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Abstract

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 ( ee s 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.

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