Genetic Engineering, Antibiotics - The Biotechnology Neomycin And Efficiency, Low Toxicity, Low-resistance, Pollution-free, Bio-pesticides-dkl

Genetic manipulation has proved to be a new way to obtain novel antibiotics, since mederrhodins were isolated from the fermentation broth of a recombination strain.Streptomyces spiramyceticus WSJ-1, a stable bioengineered strain was constructed by integrating 4"-O-isovaleryl-transferase gene (ist) through homologous recombination into the chromosome of spiramycin--producing strain Streptomyces spiramyceticus F21. The secondary metabolites of the bioengineered strain was named as Shengjimycin or Biotechmycin, which was promising and potential for pharmaceutical application, since the studies of pharmacodynamics of Shengjimycin has demonstrated that the developing hybrid antibiotic was more active against gram-positive and some gram-negative bacteria both in vivo and in vitro than 4"-O-acetylspiramycin and erythromycin, currently widely used in clinic.The first part of this dissertation is mainly on the chemical study targeted for promoting application and register of Shengjimycin as a new anti--bacteria drug.Based on different principle of separation for organic compounds, such as countercurrent distribution, basic silica gel column chromatography, preparative thin layer chromatography, vacuum liquid chromatography, etc. seven components of Shengjimycin were isolated, five of them were in pure form, one of them was composed of two isomers.By means of Spectral analysis including Ultraviolet Spectrum, FT-Infrared Spectrum, FAB-MS, HRSI--MS, ¹H-NMR, ¹³C-NMR, and 2D--NMR, such as, ¹H-¹H COSY, ¹³C-¹H COSY, and GC, GC--MS, the structures of Shengjimycin A₁, B₁, E, A_2α, A_2β, C₁, and D₁ were identified as 4"-O-isovalerylspiramycinâ…¢, 4"-O-isovalerylspiramycin â…¡, 4"-O-isovalerylspiramycin â… , 4"-O-butyrylspiramycin â…¢, 4"-O-isobutyrylspiramycin â…¢, 4"-O-acetylspiramycinâ…¢ and 4"-O-acetylspiramycinâ…¡, respectively. Shengjimycin A_2β is a novel hybrid 4"-O-acylspiramycin.The analysis of RP--HPLC demonstrated: three targeted components Shengjimycin A₁, B₁, E, the major components of shengjimycins, accounted for 55 percent of Shengjimycin complex.