食品与药品2024,Vol.26Issue(6) :526-531.DOI:10.3969/j.issn.1672-979X.2024.06.009

达巴万星前体A-40926 B0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 B0

李文科 江雪林 甘建业 董华 万传星 张仁文
食品与药品2024,Vol.26Issue(6) :526-531.DOI:10.3969/j.issn.1672-979X.2024.06.009

达巴万星前体A-40926 B0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 B0

李文科 1江雪林 2甘建业 2董华 2万传星 3张仁文2
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作者信息

  • 1. 湖北宏中药业股份有限公司,湖北黄冈 438000;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
  • 2. 湖北宏中药业股份有限公司,湖北黄冈 438000
  • 3. 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
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摘要

目的 建立达巴万星前体A-40926 B0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-40926B0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.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300r/min,空气流量为6m3/h,在此条件下A-40926 B.的产量达到3568.91 mg/L,500 L和5000 L中试罐A-40926 B0的产量分别达到3436.61,3348.25 mg/L.结论 建立了A-40926 B0的高产中试发酵工艺,可为其工业化生产提供参考.

Abstract

Objective To establish a high-yield pilot fermentation process of dalbavancin precursor A-40926 B0.Methods Nonomuraea sp.DB-3-04 was selected as the experimental strain,and the content of dalbavancin precursor A-40926 B0 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 B0 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 B0 reached 3568.91 mg/L.The yield of A-40926 B0 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 B0 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

Key words

dalbavancin/fermentation/HPLC/process optimization/pilot scale-up

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出版年

2024
食品与药品
山东省生物药物研究院

食品与药品

CSTPCD
影响因子:0.537
ISSN:1672-979X
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