Mechanistic Studies on the Conversion of Arylamines into Arylnitro Compounds by Aminopyrrolnitrin Oxygenase: Identification of Intermediates and Kinetic Studies

摘要

Rieske oxygenases are widespread in nature and catalyze a diverse set of oxidation reactions including cis-dihydroxylation, monohydroxylation, desaturation, sulfoxidation, and O- and N-dealkylation.[1], [2] Recently, we reported the characterization of a Rieske N-oxygenase, aminopyrrolnitrin oxygenase (PrnD), which catalyzes unusual arylamine oxidation reactions.[3] Although arylamine oxidases seem to be widely distributed and used in a variety of metabolic reactions,[4]-[9] PrnD represents one of only two known examples of arylamine oxidases or N-oxygenases involved in the formation of nitro groups, the other being AurF involved in aureothin biosynthesis.[9] PrnD is involved in the biosynthesis of antibiotic pyrrolnitrin[3-chloro-4-(2-nitro-3-chlorophenyl)pyrrole] (1), which is produced by many Pseudomonads and displays broad-spectrum antifungal activity.[10] In the proposed biosynthetic pathway of 1 (Scheme 1),[11] PrnD catalyzes the oxidation of the amino group of aminopyrrolnitrin (2) to a nitro group to form 1. Although PrnD has been characterized, no experimental evidence has been available for the mechanism of conversion of the arylamine. Therefore, we decided to investigate the intermediates formed during the conversion of arylamine into arylnitro compounds, as these might provide valuable mechanistic information.