Heterocyclic Aromatic N-Oxidation in the Biosynthesis of Phenazine Antibiotics from Lysobacter antibioticus

Org Lett. 2016 May 20;18(10):2495-8. doi: 10.1021/acs.orglett.6b01089. Epub 2016 May 4.

Abstract

Heterocyclic aromatic N-oxides often have potent biological activities, but the mechanism for aromatic N-oxidation is unclear. Six phenazine antibiotics were isolated from Lysobacter antibioticus OH13. A 10 gene cluster was identified for phenazine biosynthesis. Mutation of LaPhzNO1 abolished all N-oxides, while non-oxides markedly increased. LaPhzNO1 is homologous to Baeyer-Villiger flavoproteins but was shown to catazlye phenazine N-oxidation. LaPhzNO1 and LaPhzS together converted phenazine 1,6-dicarboxylic acid to 1,6-dihydroxyphenazine N5,N10-dioxide. LaPhzNO1 also catalyzed N-oxidation of 8-hydroxyquinoline.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / biosynthesis
  • Anti-Bacterial Agents / isolation & purification*
  • Bacterial Proteins / genetics
  • Biosynthetic Pathways* / genetics
  • Cyclic N-Oxides / chemistry*
  • Hydrocarbons, Aromatic / chemistry*
  • Lysobacter / enzymology
  • Lysobacter / genetics
  • Lysobacter / metabolism*
  • Mixed Function Oxygenases / genetics
  • Molecular Structure
  • Multigene Family
  • Phenazines / isolation & purification*

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Cyclic N-Oxides
  • Hydrocarbons, Aromatic
  • Phenazines
  • Mixed Function Oxygenases