Reductive biotransformation of nitroalkenes via nitroso-intermediates to oxazetes catalyzed by xenobiotic reductase A (XenA)

Abstract

A novel reductive biotransformation pathway for β,β-disubstituted nitroalkenes catalyzed by flavoproteins from the Old Yellow Enzyme (OYE) family was elucidated. It was shown to proceed via enzymatic reduction of the nitro-moiety to furnish the corresponding nitroso-alkene, which underwent spontaneous (non-enzymatic) electrocyclization to form highly strained 1,2-oxazete derivatives. At elevated temperatures the latter lost HCN via a retro-[2 + 2]-cycloaddition to form the corresponding ketones. This pathway was particularly dominant using xenobiotic reductase A, while pentaerythritol tetranitrate-reductase predominantly catalyzed the biodegradation via the Nef-pathway.

The Nitro to Carbonyl Conversion (Nef Reaction): New Perspectives for a Classical Transformation

“…Further studies performed on 2-phenyl-1-nitroprop-1-ene using xenobiotic reductase A( XenA)-NADH as well as other enzymes, showedt hat the Nef reactioni sa lmostt otally surmounted by an alternative process.R eduction of the nitroalkene to nitroso derivative 158 is followed by intramolecular ring closure to oxazete 159 (Scheme 51). [107] Oxazete 159 is partially converted into acetophenone through acycloreversion which also releases HCN.…”

The Enzymology of Organic Transformations: A Survey of Name Reactions in Biological Systems

“…The following OYE-type enzymes had been shown to have the capability to catalyze the conversion of ( E/Z )-1-nitro-2-phenyl-1-propene ( 206 ) to the corresponding oxime and aldehyde (Figure 53c): xenobiotic reductases A and B from Pseudomonas putida , 12-oxophytodienoic acid reductase (OPR3) from Lycopersicon esculentum , pentaerythritol teranitrate reductase (PETN-R) from Enterobacter cloacae , glycerol teranitrate reductase (NerR) from Agrobacterium radiobacter , and morphinone reductase (MorR) as well as quinone reductase (YhdA) from unnamed sources. [190] These enzyme-catalyzed degradations of nitroalkanes have been proposed to proceed via the mechanism of Nef reaction, involving the formation of an oxime intermediate.…”

An enoate reductase Achr-OYE4 from Achromobacter sp. JA81: characterization and application in asymmetric bioreduction of C=C bonds

“…PETN reductase catalyzes β,β-disubstituted nitroalkenes to form carbonyl compound, predominantly through the Nef-pathway (Durchschein et al 2010), whereas XenA is effective in oxazete formation (Durchschein et al 2011). In the biotransformation of 5a catalyzed with Achr-OYE4, the expected reductive product 5b might undergo an elimination process to form 5c (Fig.…”