吸水链霉菌ATCC 29253产Hygrocin A发酵条件的优化

【背景】Hygrocins是一种萘安莎抗生素,具有良好的新药开发潜能。但在常见培养基及发酵条件下菌体内Hygrocin A含量一般很低,甚至难以直接进行准确检测。【目的】提高吸水链霉菌ATCC 29253发酵物中Hygrocin A的产量。【方法】采用单因素与正交试验设计优化相结合的方法系统考察碳源、氮源、磷酸盐、MgCl_2浓度、NaCl浓度、种子菌龄等因素对吸水链霉菌ATCC 29253产Hygrocin A能力的影响。【结果】最佳发酵条件为(g/L):葡萄糖4.0,黄豆饼粉8.0,麦芽提取物10.0,K_2HPO_4 1.5,KH_2PO_4 1.5,NaCl 1.5,Mg Cl2 1.0;种子最佳活化时间为48 h;培养参数:摇床转速200 r/min,初始pH为6.8-7.0,瓶装量50 m L/250 m L,接种量5%,30°C培养10 d。在优化条件下,Hygrocin A产量与其原始培养基M10相比提高了500%,Rapamycin产量同时下降了95%。【结论】通过培养基优化,可显著提高吸水链霉菌ATCC 29253中Hygrocin A产量,为Hygrocin A合成应用研究奠定基础,同时可使Rapamycin产量明显下降。这说明可通过选择培养条件有目的地调节两种抗生素的代谢通量,进而开展多种抗生素同时表达的代谢调控研究。

Optimization of fermentation conditions for Hygrocin A production by Streptomyces hygroscopicus ATCC 29253

[Background] Hygrocins, a kind of naphthalene ansa antibiotics, are potential leading compounds for the chemical biosynthesis of novel drugs. However, under the common medium and fermentation conditions, the content of Hygrocin A in the cell is generally very low, and it is difficult to detect it directly. [Objective] In order to improve the yield of Hygrocin A from Streptomyces hygroscopicus ATCC 29253. [Methods] Effects of carbon source, nitrogen source, phosphate concentration, MgCl2 concentration, NaCl concentration and seed age on Hygrocin A production from S. hygroscopicus ATCC 29253 were studied by single factor and orthogonal test design. [Results] The optimal fermentation conditions were as follows: glucose 4.0 g/L, soybean cake meal 8.0 g/L, malt extract 10.0 g/L, K2HPO4 1.5 g/L, KH2PO4 1.5 g/L, NaCl 1.5 g/L, MgCl2 1.0 g/L; seed age 48 h; culture parameters: shaking speed 200 r/min, pH 6.8?7.0, bottled in 50 mL/250 mL, inoculated quantity 5%, incubated at 30 °C for 10 days. Under optimized conditions, the yield of Hygrocin A increased 500%, compared with its original medium M10, whereas at the same time the yield of Rapamycin decreased 95%. [Conclusion] The yield of Hygrocin A from S. hygroscopicus ATCC 29253 was significantly improved by optimizing the fermentation medium, which lay the foundation for studying the synthesis and application of Hygrocin A. At the same time, the yield of Rapamycin decreased significantly. This suggests that the metabolic flux of the two antibiotics can be adjusted intentionally by selecting the culture conditions, and then the metabolic regulation research for simultaneous expression of multiple antibiotics can be carried out.