Unusual Activities of the Thioesterase Domain for the Biosynthesis of the Polycyclic Tetramate Macrolactam HSAF in <i>Lysobacter enzymogenes</i> C3

HSAF is an antifungal natural product with a new mode of action. A rare bacterial iterative PKS-NRPS assembles the HSAF skeleton. The biochemical characterization of the NRPS revealed that the thioesterase (TE) domain possesses the activities of both a protease and a peptide ligase. Active site mutagenesis, circular dichroism spectra, and homology modeling of the TE structure suggested that the TE may possess uncommon features that may lead to the unusual activities. The iterative PKS-NRPS is found in all polycyclic tetramate macrolactam gene clusters, and the unusual activities of the TE may be common to this type of hybrid PKS-NRPS

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

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