Heterocyclic Aromatic <i>N</i>‑Oxidation in the Biosynthesis of Phenazine Antibiotics from Lysobacter antibioticus

Abstract

Heterocyclic aromatic <i>N</i>-oxides often have potent biological activities, but the mechanism for aromatic <i>N</i>-oxidation is unclear. Six phenazine antibiotics were isolated from Lysobacter antibioticus OH13. A 10 gene cluster was identified for phenazine biosynthesis. Mutation of <i>LaPhzNO1</i> abolished all <i>N</i>-oxides, while non-oxides markedly increased. LaPhzNO1 is homologous to Baeyer–Villiger flavoproteins but was shown to catazlye phenazine <i>N</i>-oxidation. LaPhzNO1 and LaPhzS together converted phenazine 1,6-dicarboxylic acid to 1,6-dihydroxyphenazine <i>N</i>5,<i>N</i>10-dioxide. LaPhzNO1 also catalyzed <i>N</i>-oxidation of 8-hydroxyquinoline