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Structure‐Based Insight into the Asymmetric Bioreduction of the CC Double Bond of α,β‐Unsaturated Nitroalkenes by Pentaerythritol Tetranitrate Reductase
Author(s) -
Toogood Helen S.,
Fryszkowska Anna,
Hare Victoria,
Fisher Karl,
Roujeinikova Anna,
Leys David,
Gardiner John M.,
Stephens Gill M.,
Scrutton Nigel S.
Publication year - 2008
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.200800561
Subject(s) - chemistry , substrate (aquarium) , enantiomeric excess , stereochemistry , aryl , yield (engineering) , active site , reductase , hydride , alkyl , enzyme , organic chemistry , enantioselective synthesis , catalysis , metal , oceanography , materials science , geology , metallurgy
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.