达巴万星前体A-40926 B_(0)的发酵工艺优化及中试放大  

Optimization and Pilot Scale-up of Fermentation Process of Dalbavancin Precursor A-40926 B_(0)

作　　者：李文科 江雪林 甘建业 董华 万传星[2] 张仁文 LI Wen-ke;JIANG Xue-lin;GAN Jian-ye;DONG Hua;WAN Chuan-xing;ZHANG Ren-wen(Hubei Honch Pharmaceutical Co.,Ltd.,Huanggang 438000,China;State Key Laboratory Breeding Base for the Protection and Utilization of Biological Resources in Tarim Basin Co-funded by Xinjiang Production&Construction Corps and The Ministry of Science&Technology/College of Life Science and Technology,Tarim University,Alar 843300,China)

机构地区：[1]湖北宏中药业股份有限公司,湖北黄冈438000 [2]塔里木盆地生物资源保护利用兵团重点实验室-省部共建国家重点实验室培育基地/塔里木大学生命科学与技术学院,新疆阿拉尔843300

出　　处：《食品与药品》2024年第6期526-531,共6页Food and Drug

基　　金：国家自然科学基金项目(编号:32060023)。

摘　　要：目的建立达巴万星前体A-40926 B_(0)的高产中试发酵工艺。方法以野野村放线菌Nonomuraea sp.DB-3-04为试验菌株,采用高效液相色谱(HPLC)测定发酵液中达巴万星前体A-40926 B_(0)的含量,考察pH值、发酵温度、溶解氧浓度、接种量和补料工艺对200 L试验罐中A-40926 B_(0)产量的影响。将200 L试验罐发酵参数放大至500 L、5000 L中试罐,进行逐级放大发酵试验。结果200 L试验罐最佳控制条件为:培养72 h后pH维持在7.5左右,培养温度为28℃,溶解氧浓度不低于50%,接种量9%,搅拌速度300 r/min,空气流量为6 m3/h,在此条件下A-40926 B_(0)的产量达到3568.91 mg/L,500 L和5000 L中试罐A-40926 B_(0)的产量分别达到3436.61,3348.25 mg/L。结论建立了A-40926 B_(0)的高产中试发酵工艺,可为其工业化生产提供参考。Objective To establish a high-yield pilot fermentation process of dalbavancin precursor A-40926 B_(0).Methods Nonomuraea sp.DB-3-04 was selected as the experimental strain,and the content of dalbavancin precursor A-40926 B_(0) in the fermentation broth was determined by HPLC.The effects of pH,fermentation temperature,dissolved oxygen,inoculation amount and feeding process on the yield of A-40926 B_(0) in 200 L fermenter tank were investigated.The fermentation parameters of 200 L fermenter tank were amplified to 500 L and 5000 L pilot tanks,and the step by step amplification fermentation experiments were carried out.Results The optimum fermentation conditions of 200 L test tank were as follows:the pH was maintained at about 7.5 after 72 h of incubation,the culture temperature was 28℃,the dissolved oxygen was not less than 50%,the inoculation amount was 9%,the stirring speed was 300 r/min,the aeration volume was 6 m3/h,and the yield of A-40926 B_(0) reached 3568.91 mg/L.The yield of A-40926 B_(0) in 500 L and 5000 L pilot tanks reached 3436.61 mg/L and 3348.25 mg/L,respectively.Conclusion The high-yield pilot fermentation process of A-40926 B_(0) is successfully established,which can provide reference for its industrial production.

关 键 词：达巴万星前体 发酵 高效液相色谱 工艺优化 中试放大 

分 类 号：TQ92[轻工技术与工程—发酵工程]