达托霉素产生菌前体物耐受选育及其流加补料发酵

目的 通过对达托霉素产生菌进行诱变选育，以及前体物补料发酵方式提高达托霉素的产量。方法 采用常压室温等离子体(atmospheric and room temperature plasma, ARTP)技术对玫瑰孢链霉菌进行诱变，以癸酸铵和甘氨酸耐受作为选择压力进行菌株筛选，在摇瓶和100L发酵罐上进行癸酸铵流加补料试验确定最佳的发酵工艺。结果 经诱变选育获得1株突变株FIM-D1568摇瓶效价达到380mg/L，发酵单位较出发菌株提高了35.7%；通过优化100L发酵罐流加补料癸酸铵溶液工艺，使达托霉素发酵效价达到2276mg/L。结论 以ARTP为诱变源，甘氨酸及癸酸铵耐受性为选择性压力，可以快速筛选获得达托霉素高产菌；高产突变菌株在流加补料发酵工艺上优良性状得以发挥，发酵效价大幅提高。

Precursor resistance screening on mutation breeding and fed-batch fermentation for daptomycin production

Objective Resistance screening on mutation breeding and fed-batch fermentation were studied to improve production of daptomycin. Methods Streptomyces roseosporus, a daptomycin-producing strain was bred by mutation of atmospheric and room temperature plasma (ARTP), with ammonium decanoate and glycine as selection factors. Adding precursor ammonium decanoate for fermentation of daptomycin were researched in a 100L fermentor. Results A mutant strain named FIM-D1568 was obtained and the yield of daptomycin reached 380mg/L which was 35.7% higher than that of the original one. Additionally, the yield of daptomycin reached 2276mg/L in a 100L fermentor by the optimization of feeding ammonium decanoate. Conclusion ARTP in combination with ammonium decanoate and glycine resistance screening can effectively improve the daptomycin production of