CIESC Journal ›› 2012, Vol. 63 ›› Issue (8): 2531-2537.DOI: 10.3969/j.issn.0438-1157.2012.08.027

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Effect of aminocyclitol compounds validamycin on fermentation of acarbose

QIN Junwei1,2,XUE Yaping1,2,ZHENG Yuguo1,2   

  • Received:2012-01-05 Revised:2012-03-19 Online:2012-08-05 Published:2012-08-05
  • Supported by:

    China National Special Program for Key Science and Technology;Special Program for KeyScience and Technology of Zhejiang;the National Natural Science Foundation

氨基环醇类化合物有效霉素对阿卡波糖发酵过程的影响

秦俊伟1,2,薛亚平1,2,郑裕国1,2   

  1. 1浙江工业大学生物与环境学院,浙江 杭州 310014:2浙江工业大学生物工程研究所,浙江 杭州 310014
  • 通讯作者: 郑裕国
  • 基金资助:

    国家重大新药创制重大科技专项;浙江省重大科技专项项目;国家自然科学基金

Abstract: Acarbose,a potent a-glucosidase inhibitor,is one of the most popular drugs for the treatment of non-insulin-dependent diabetes.Currently most investigations focus on increasing the acarbose titer and decreasing the production of byproduct.The effect of aminocyclitol compound validamycin on the fermentation process of acarbose was investigated.It was deduced that validamycin not only enhanced the consumption of carbohydrate,the growth of cell and the accumulation of acarbose,but also inhibited the generation of byproduct component C.A fed-batch fermentation strategy that added an appropriate amount of nitrogen and carbon source in 72 h and 96 h after inoculation was adopted with the addition of 0.08 g·L-1 validamycin A into the medium.As a result,the maximum acarbose titer reached 5602 mg·L-1,increasing by 57% compared with the control,and the byproduct component C decreased by 54% simultaneously.

Key words: acarbose, validamycin, component C, fermentation

摘要: 阿卡波糖是目前最有效的治疗Ⅱ型糖尿病的糖苷酶抑制剂类药物之一。提高阿卡波糖发酵水平,并减少其发酵副产物的合成是研究的难点。利用Actinoplanes utahensis ZJB-08196产阿卡波糖突变株,通过摇瓶发酵,研究了氨基环醇类化合物有效霉素对阿卡波糖发酵过程的影响。研究结果表明,有效霉素A能有效促进阿卡波糖发酵过程中的糖类消耗,有利于菌体生长,提高阿卡波糖的发酵水平,同时有效地抑制组分C的生成,减轻下游分离的难度。当发酵培养基中有效霉素A浓度为0.08 g·L-1,并且在中期添加氮源和碳源的补料发酵过程中,阿卡波糖的发酵水平达到5602 mg·L-1,相比对照提高了57%,产生的组分C与对照相比降低了54%。

关键词: 阿卡波糖, 有效霉素, 组分C, 发酵