Journal
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
Volume 508, Issue 1, Pages 39-45Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2011.01.010
Keywords
Arylamine oxygenase; Diiron enzyme; AurF; Aminophenols; Non-ribosomal peptide synthetase
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Funding
- Camille & Henry Dreyfus faculty startup award
- Rose Hills summer research award
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The regiospecific oxidation of aromatic amines to aryl nitro compounds is critical to the synthesis of several natural products having pharmacological importance. The arylamine N-oxygenase (AAO) from Streptomyces thioluteus (AurF) selectively oxidizes p-aminobenzoic acid to p-nitrobenzoic acid and has been the subject of investigation for its unique chemistry and substrate preferences. Little, however, is known about the biochemistry and substrate specificities of AurF homologues, which are often associated with non-ribosomal peptide synthetases or polyketide synthases and have substrate binding pockets with substantially different amino acid compositions based on sequence alignments. An AAO homolog from Pseudomonas syringae pv. phaseolicola was expressed and purified to further explore the substrate specificity and biosynthetic utility of this enzyme class. PsAAO-was most active on substituted o-aminophenols at pH 9 in buffer solutions containing 40% methanol. o-Aminophenols allow both the Pseudomonas and Streptomyces AAOs to act on para-substituted arylamines having methoxy, methyl, and nitro groups, which was previously unseen. A Hammett plot of k(cat,app) VS. sigma has a rho = 1.5, indicating substrate reactivity is dependent on the electron donating effects of substituents. The mechanistic data are consistent with an amine lone pair attacking an activated oxygen atom after formation of the hydroperoxy Fe-III/III intermediate. (C) 2011 Elsevier Inc. All rights reserved.
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