甲基化试剂对螺旋霉素发酵的影响

Effects of Methylation Reagent on Spiramycin Fermentation

研究了在发酵过程中添加氯化胆碱对发酵产螺旋霉素及组分的影响。采用单因子实验设计法,以效价和杂质组分为指标,优化氯化胆碱的添加条件。结果表明,氯化胆碱的最优添加时间为120 h、最优添加浓度为0.66 g.L-1,在此条件下发酵效价提高约15%,各主要杂质组分的含量均降低,其中杂质UNK4的含量变化最显著,而有效组分的含量相应有所提升。中间代谢物测定结果显示,氯化胆碱的添加增加了乙酸等前体物质的浓度,有助于增大TCA循环通量,促进螺旋霉素的合成。15 L罐放大结果表明,该工艺有工业应用前景。

Effects of supplementing choline chloride for spiramycin fermentation and components by Streptomyces ambofaciens were studied.Based on titer and impurities,the conditions to supplement choline chloride were optimized by one-factor-design.The results showed that the titer was increased about 15% and the primary impurities were decreased by supplementing 0.66 g·L-1 choline chloride at 120 h,among which UNK4 was most decreased.Meanwhile,content of the active component was correspondingly increased.It also showed that the concentration of the macrolide precursor such as acetic acid which was helpful to enhance the TCA circulation flux has increased after addition,resulting in the promoted spriamycin production.The results on 15 L fermenter showed that this method could be expand for industrial process.