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Folia Microbiologica

, Volume 56, Issue 6, pp 555–561 | Cite as

Mutational biosynthesis of neomycin analogs by a mutant of neomycin-producing Streptomyces fradiae

  • Guanying Shi
  • Xingang Zhang
  • Lang Wu
  • Jin Xie
  • Ke Tao
  • Taiping HouEmail author
Article

Abstract

Neomycin, produced by Streptomyces fradiae, has been widely used for the treatment of bacterial infections in clinical and agricultural applications. In this study, a neomycin nonproducing mutant of S. fradiae was obtained by gene disruption technique for mutational biosynthesis. A crucial gene neoC (neo7) which encodes 2-deoxystreptamine (2-DOS) synthases was disrupted. The mutant could resume producing neomycin in the presence of 2-DOS. Salen derivatives of 2-DOS were synthesized and individually added to cultures of the mutant. Antibacterial activity of the mutasynthesis products against Staphylococcus aureus and four plant pathogenic bacteria (Pseudomonas solanacarum, Erwinia carotovora, Xanthomonas oryzae, and Xanthomonas campestris) was detected quantitatively by Oxford cup method. It is suggested that all 2-DOS derivatives were incorporated by the mutant into new active neomycin analogs except for 2-DOS derivative 2d ((1R,2r,3S,4R,6S)-4,6-bis((E)-3,5-di-tert-butyl-2-hydroxybenzylideneamino)cyclohexane-1,2,3-triol). Neomycin analogs produced by feeding 2-DOS derivative 2a ((1R,2r,3S,4R,6S)-4,6-bis((E)-2 hydroxybenzylideneamino)cyclohexane-1,2,3-triol) to cultures of the mutant displayed a similar antibacterial activity with neomycin produced by wild strain.

Keywords

Neomycin Fermentation Product Wild Strain Biosynthetic Gene Cluster Aminoglycoside Antibiotic 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

This project was supported by grants from the National Natural Science Foundation of China (no. 30800034), the Science and Technology Department 11th Five-year Plan, State Science and Technology support projects (no. 2006BAE01A01-14), and the National High Technology Research and Development Program of China (863 Program, No. 2009AA032903). The authors also thank the Analytical Detective Center and Pharmaceutical School of Sichuan University for the NMR spectroscopic analysis.

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Copyright information

© Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i. 2011

Authors and Affiliations

  • Guanying Shi
    • 1
    • 2
  • Xingang Zhang
    • 1
    • 2
  • Lang Wu
    • 1
    • 2
  • Jin Xie
    • 2
  • Ke Tao
    • 2
  • Taiping Hou
    • 1
    • 2
    Email author
  1. 1.Key Laboratory of Bio-Resource and Eco-Environment of Ministry of EducationSichuan UniversityChengduPeople’s Republic of China
  2. 2.College of Life SciencesSichuan UniversityChengduPeople’s Republic of China

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