【摘要】 Microcin B17(简称MccB17)是核糖体合成的肽类DNA螺旋酶抑制剂,其独特的分子结构是抗菌剂未来发展的重要的新颖结构,MccB17产生菌的杂环形成机理对于制药工业的药物设计具有重要意义。MccB17产生菌E.coliZB43适宜在M63合成培养基中积累胞内MccB17,低溶氧水平利于MccB17的积累。当葡萄糖浓度超过1g/L时,MccB17的合成受到阻遏。采用均匀设计表U11(1110)进行发酵培养基配比调整,确定了最佳的含葡萄糖合成培养基配比:葡萄糖1g/L,KH2PO43g/L,K2HPO47g/L,(NH4)2SO41g/L,MgSO4.7H2O 1.8mmol/L,盐酸硫胺1.8μg/ml。丁二酸钠能解除葡萄糖对E.coliZB43生成MccB17的代谢阻遏。以10g/L丁二酸钠替代葡萄糖为唯一碳源,在上述最佳发酵培养基配比条件下,37℃24h,MccB17的产量可达559.6μg/ml。更多还原

【Abstract】 Microcin B17（MccB17） is a ribosomally synthesized peptide antibiotic,which inhibits its cellular target,DNA gyrase.Since its unique heterocycle-containing structure is so often found to be antitumour,antiviral or antibiotic in nature,MccB17 may prove to be a novel lead structure for the further general development of antimicrobial agents.The thiazole and oxazole ring-forming mechanisms found in MccB17 producing bacteria could prove to be a novel way of introducing new mimetic structure into peptides for use in the pharmaceutical industry.Results show MccB17 producing strain E.coli ZB43 accumulated more MccB17 in medium M63 than in medium LB.In shake flask,oxygen limitation improved the yield of MccB17.Glucose was repressive at the concentration over than 1g/L.The concentrations of fermentation medium,with glucose as carbon source,was optimized by uniform design U₁₁(11¹⁰).The obtained optimal medium ingredients are:glucose 1g/L,KH₂PO₄ 3g/L,K₂HPO₄ 7g/L,（NH₄）₂SO₄ 1g/L,MgSO₄·7H₂O 1.8mmol/L,thiamine 1.8μg/ml.Moreover,results show that succinate is an excellent carbon source for production of MccB17,which released the repression of glucose.When glucose was replace by succinate（10g/L） as sole carbon source in the optimal fermentation medium,at 37℃,the production yield of MccB17 reached 559.6μg/ml after fermentation for 24h.更多还原