title: Novel nikkomycin analogues generated by mutasynthesis in Streptomyces ansochromogenes.
abstract: BACKGROUND
  Nikkomycins are competitive inhibitors of chitin synthase and inhibit the growth of filamentous fungi, insects, acarids and yeasts. The gene cluster responsible for biosynthesis of nikkomycins has been cloned and the biosynthetic pathway was elucidated at the genetic, enzymatic and regulatory levels.
  
  
  RESULTS
  Streptomyces ansochromogenes ΔsanL was constructed by homologous recombination and the mutant strain was fed with benzoic acid, 4-hydroxybenzoic acid, nicotinic acid and isonicotinic acid. Two novel nikkomycin analogues were produced when cultures were supplemented with nicotinic acid. These two compounds were identified as nikkomycin Px and Pz by electrospray ionization mass spectrometry (ESI-MS) and nuclear magnetic resonance (NMR). Bioassays against Candida albicans and Alternaria longipes showed that nikkomycin Px and Pz exhibited comparatively strong inhibitory activity as nikkomycin X and Z produced by Streptomyces ansochromogenes 7100 (wild-type strain). Moreover, nikkomycin Px and Pz were found to be more stable than nikkomycin X and Z at different pH and temperature conditions.
  
  
  CONCLUSIONS
  Two novel nikkomycin analogues (nikkomycin Px and Pz) were generated by mutasynthesis with the sanL inactivated mutant of Streptomyces ansochromogenes 7100. Although antifungal activities of these two compounds are similar to those of nikkomycin X and Z, their stabilities are much better than nikkomycin X and Z under different pHs and temperatures.
authors.forename: Chi
authors.initials: C
authors.lastname: Feng
authors.forename: Hongbo
authors.initials: H
authors.lastname: Ling
authors.forename: Deyao
authors.initials: D
authors.lastname: Du
authors.forename: Jihui
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, NO,1 Beichen West Road, Chaoyang District, Beijing 100101, China. niugq@im.ac.cn.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Niu
authors.forename: Huarong
authors.initials: H
authors.lastname: Tan
mesh_terms: D000528:Alternaria / Q000187:drug effects; D000617:Aminoglycosides / Q000096:biosynthesis* / Q000737:chemistry / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects; D004151:Dipeptides / Q000096:biosynthesis* / Q000302:isolation & purification / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D005810:Multigene Family; D009154:Mutation; D009525:Niacin / Q000494:pharmacology; D009705:Nucleosides / Q000096:biosynthesis* / Q000302:isolation & purification / Q000494:pharmacology; D013302:Streptomyces / Q000187:drug effects / Q000378:metabolism*; D053719:Tandem Mass Spectrometry; D013696:Temperature; D000637:Transaminases / Q000235:genetics; D014529:Uridine / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000302:isolation & purification / Q000494:pharmacology
chemical_list: D000617:Aminoglycosides; D004151:Dipeptides; D009705:Nucleosides; C000592547:nikkomycin Px; C000592548:nikkomycin Pz; D009525:Niacin; C011952:nikkomycin; D000637:Transaminases; C113111:lysine 2-aminotransferase; D014529:Uridine
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