title: Novel polyoxins generated by heterologously expressing polyoxin biosynthetic gene cluster in the sanN inactivated mutant of Streptomyces ansochromogenes.
abstract: BACKGROUND
  Polyoxins are potent inhibitors of chitin synthetases in fungi and insects. The gene cluster responsible for biosynthesis of polyoxins has been cloned and sequenced from Streptomyces cacaoi and tens of polyoxin analogs have been identified already.
  
  
  RESULTS
  The polyoxin biosynthetic gene cluster from Streptomyces cacaoi was heterologously expressed in the sanN inactivated mutant of Streptomyces ansochromogenes as a nikkomycin producer. Besides hybrid antibiotics (polynik A and polyoxin N) and some known polyoxins, two novel polyoxin analogs were accumulated. One of them is polyoxin P that has 5-aminohexuronic acid with N-glycosidically bound thymine as the nucleoside moiety and dehydroxyl-carbamoylpolyoxic acid as the peptidyl moiety. The other analog is polyoxin O that contains 5-aminohexuronic acid bound thymine as the nucleoside moiety, but recruits polyoximic acid as the sole peptidyl moiety. Bioassay against phytopathogenic fungi showed that polyoxin P displayed comparatively strong inhibitory activity, whereas the inhibitory activity of polyoxin O was weak under the same testing conditions.
  
  
  CONCLUSIONS
  Two novel polyoxin analogs (polyoxin P and O) were generated by the heterologous expression of polyoxin biosynthetic gene cluster in the sanN inactivated mutant of Streptomyces ansochromogenes. Polyoxin P showed potent antifungal activity,while the activity of polyoxin O was weak. The strategy presented here may be available for other antibiotics producers.
authors.affiliation: State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Jine
authors.initials: J
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.forename: Chi
authors.initials: C
authors.lastname: Feng
authors.forename: Yihua
authors.initials: Y
authors.lastname: Chen
authors.forename: Huarong
authors.initials: H
authors.lastname: Tan
mesh_terms: D000617:Aminoglycosides / Q000096:biosynthesis; D000935:Antifungal Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D005658:Fungi / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D005810:Multigene Family; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D011741:Pyrimidine Nucleosides / Q000096:biosynthesis / Q000737:chemistry / Q000494:pharmacology; D013302:Streptomyces / Q000235:genetics / Q000378:metabolism*; D053719:Tandem Mass Spectrometry
chemical_list: D000617:Aminoglycosides; D000935:Antifungal Agents; D011741:Pyrimidine Nucleosides; C580568:polyoxin O; C580569:polyoxin P; C002457:polyoxin; C011952:nikkomycin