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Media type:
E-Article
Title:
Four-electron oxidation of p -hydroxylaminobenzoate to p -nitrobenzoate by a peroxodiferric complex in AurF from Streptomyces thioluteus
Contributor:
Li, Ning;
Korboukh, Victoria Korneeva;
Krebs, Carsten;
Bollinger, J. Martin
imprint:
Proceedings of the National Academy of Sciences, 2010
Published in:Proceedings of the National Academy of Sciences
Language:
English
DOI:
10.1073/pnas.1002785107
ISSN:
1091-6490;
0027-8424
Origination:
Footnote:
Description:
<jats:p>
The nonheme di-iron oxygenase, AurF, converts
<jats:italic>p</jats:italic>
-aminobenzoate (Ar-NH
<jats:sub>2</jats:sub>
, where Ar = 4-carboxyphenyl) to
<jats:italic>p</jats:italic>
-nitrobenzoate (Ar-NO
<jats:sub>2</jats:sub>
) in the biosynthesis of the antibiotic, aureothin, by
<jats:italic>Streptomyces thioluteus</jats:italic>
. It has been reported that this net six-electron oxidation proceeds in three consecutive, two-electron steps, through
<jats:italic>p</jats:italic>
-hydroxylaminobenzoate (Ar-NHOH) and
<jats:italic>p</jats:italic>
-nitrosobenzoate (Ar-NO) intermediates, with each step requiring one equivalent of O
<jats:sub>2</jats:sub>
and two exogenous reducing equivalents. We recently demonstrated that a peroxodiiron(III/III) complex (peroxo-
<jats:inline-formula>
<jats:inline-graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="pnas.1002785107eq1.gif" />
</jats:inline-formula>
-AurF) formed by addition of O
<jats:sub>2</jats:sub>
to the diiron(II/II) enzyme (
<jats:inline-formula>
<jats:inline-graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="pnas.1002785107eq2.gif" />
</jats:inline-formula>
-AurF) effects the initial oxidation of Ar-NH
<jats:sub>2</jats:sub>
, generating a μ-(oxo)diiron(III/III) form of the enzyme (
<jats:italic>μ</jats:italic>
-oxo-
<jats:inline-formula>
<jats:inline-graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="pnas.1002785107eq3.gif" />
</jats:inline-formula>
-AurF) and (presumably) Ar-NHOH. Here we show that peroxo-
<jats:inline-formula>
<jats:inline-graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="pnas.1002785107eq4.gif" />
</jats:inline-formula>
-AurF also oxidizes Ar-NHOH. Unexpectedly, this reaction proceeds through to the Ar-NO
<jats:sub>2</jats:sub>
final product, a four-electron oxidation, and produces
<jats:inline-formula>
<jats:inline-graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="pnas.1002785107eq5.gif" />
</jats:inline-formula>
-AurF, with which O
<jats:sub>2</jats:sub>
can combine to regenerate peroxo-
<jats:inline-formula>
<jats:inline-graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="pnas.1002785107eq6.gif" />
</jats:inline-formula>
-AurF. Thus, conversion of Ar-NHOH to Ar-NO
<jats:sub>2</jats:sub>
requires only a single equivalent of O
<jats:sub>2</jats:sub>
and (starting from
<jats:inline-formula>
<jats:inline-graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="pnas.1002785107eq7.gif" />
</jats:inline-formula>
-AurF or peroxo-
<jats:inline-formula>
<jats:inline-graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="pnas.1002785107eq8.gif" />
</jats:inline-formula>
-AurF) is fully catalytic in the absence of exogenous reducing equivalents, by contrast to the published stoichiometry. This novel type of four-electron
<jats:italic>N</jats:italic>
-oxidation is likely also to occur in the reaction sequences of nitro-installing di-iron amine oxygenases in the biosyntheses of other natural products.
</jats:p>