天然产物研究与开发 ›› 2015, Vol. 27 ›› Issue (3): 398-403.doi: 10.16333/j.1001-6880.2015.03.006

• 研究论文 • 上一篇    下一篇

赭曲霉转化洋地黄毒苷的工艺优化和产物活性分析

骆健美1*,宋霆1,朱凤芝1,申雁冰1,李景新2,王敏1   

  1. 1 工业发酵微生物教育部重点实验室 天津市工业微生物重点实验室 天津科技大学生物工程学院,天津 300457;2 山东大学医学院生理研究所,济南 250012
  • 出版日期:2015-03-30 发布日期:2015-04-07

Optimization on Biotransformation Technology of Digitoxin by Aspergillus ochraceus and the Products Activity Analysis

LUO Jian-mei1*, SONG Ting1, ZHU Feng-zhi1, SHEN Yan-bing1, LI Jing-xin2, WANG Min1   

  1. 1 Key Laboratory of Industrial Fermentation Microbiology,Ministry of Education,Tianjin Key Lab of Industrial Microbiology,College of Biotechnology,Tianjin University of Science and Technology,Tianjin 300457,China; 2 Department of Physiology School of Medicine Shandong University,Jinan 250012,China
  • Online:2015-03-30 Published:2015-04-07

摘要: 以赭曲霉Rn405转化洋地黄毒苷的微生物转化工艺为研究对象,对助溶剂种类、底物浓度、金属离子种类和浓度等关键参数进行优化,确定的最优转化条件为:发酵培养基中添加1 mmol/L Mn2+离子,28 ℃,180 rpm振荡培养28 h时加入溶解于DMSO的底物溶液,使其终浓度为100 mg/L,然后在相同的条件下转化96 h。此时,底物的转化率和11α-羟基洋地黄毒苷元的生成率分别达到了100%和25.4%,比优化前分别提高了33.1%和14.5%。通过斯氏灌流法和Langendorff灌流法,探讨两个转化产物对蟾蜍和大鼠心肌细胞收缩能力的影响。结果表明,洋地黄毒苷元对心肌细胞收缩率的影响和底物洋地黄毒苷相当,而11α-羟基洋地黄毒苷元对心肌细胞收缩率的影响比底物洋地黄毒苷和洋地黄毒苷元均有所增强。

关键词: 赭曲霉, 洋地黄毒苷, 微生物转化, 工艺优化, 活性分析

Abstract: In this study,the key parameters in the biotransformation process of digitoxin by Aspergillus ochraceus  Rn405 were optimized,including the type of cosolvent, substrate concentration,the type and concentration of metal ions.The optimal biotransformation conditions were as follows:1 mmol/L Mn2+ was added into the fermentation medium,the cells was grown at 28 °C on a rotary shaker (180 rpm) for 28 h and then the substrate dissolved in DMSO was added to the final concentration of 100 mg/L,and the biotransformation process lasted for 96 h at the same condition.At this point,the conversion ratio of substrate and the generation ratio of 11α-gitoxigenin were 100% and 25.4%,respectively,which was increased by 33.1% and 14.5% compared with original condition.The effects of the two biotransformation products on the myocardial contractility of bufo and rats were investigated using Smith’s perfusion method and Langendorff perfusion method.The results indicated that the product digitoxigenin had the same impact on myocardial cell shrinkage as the substrate digitoxin,while the influence of another product 11α-hydroxy-dgitoxigenin on myocardial cell shrinkage was enhanced compared with the substrate digitoxin and the product digitoxigenin.

Key words: Aspergillus ochraceus, digitoxin, microbial transformation, process optimization, activity analysis

中图分类号: 

Q963