Four-electron oxidation of p-hydroxylaminobenzoate to p-nitrobenzoate by a peroxodiferric complex in AurF from Streptomyces thioluteus

Ning Li, Victoria Korneeva Korboukh, Carsten Krebs, J. Martin Bollinger

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The nonheme di-iron oxygenase, AurF, converts p-aminobenzoate (Ar-NH2, where Ar = 4-carboxyphenyl) to p-nitrobenzoate (Ar-NO2) in the biosynthesis of the antibiotic, aureothin, by Streptomyces thioluteus. It has been reported that this net six-electron oxidation proceeds in three consecutive, two-electron steps, through p-hydroxylaminobenzoate (Ar-NHOH) and p-nitrosobenzoate (Ar-NO) intermediates, with each step requiring one equivalent of O2 and two exogenous reducing equivalents. We recently demonstrated that a peroxodiiron(III/III) complex (peroxo-Fe2 III/III-AurF) formed by addition of O2 to the diiron(II/II) enzyme (Fe2II/II-AurF) effects the initial oxidation of Ar-NH2, generating a μ-(oxo)diiron (III/III) form of the enzyme (μ-oxo-Fe2III/III-AurF) and (presumably) Ar-NHOH. Here we show that peroxo-Fe2III/III-AurF also oxidizes Ar-NHOH. Unexpectedly, this reaction proceeds through to the Ar-NO 2 final product, a four-electron oxidation, and produces Fe 2II/II-AurF, with which O2 can combine to regenerate peroxo-Fe2III/III-AurF. Thus, conversion of Ar-NHOH to Ar-NO2 requires only a single equivalent of O2 and (starting from Fe2II/II-AurF or peroxo-Fe 2III/III-AurF) is fully catalytic in the absence of exogenous reducing equivalents, by contrast to the published stoichiometry. This novel type of four-electron N-oxidation is likely also to occur in the reaction sequences of nitro-installing di-iron amine oxygenases in the biosyntheses of other natural products.

Original languageEnglish (US)
Pages (from-to)15722-15727
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number36
StatePublished - Sep 7 2010


All Science Journal Classification (ASJC) codes

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