波赛链霉菌dnrK基因中断突变株代谢产物鉴定

发布时间：2018-01-05 10:01

  本文关键词：波赛链霉菌dnrK基因中断突变株代谢产物鉴定　出处：《中国抗生素杂志》2015年11期 　论文类型：期刊论文

  更多相关文章： 波赛链霉菌 dnrK Histomodulin 基因中断

【摘要】：目的鉴定波赛链霉菌HS062(柔红霉素工业菌株)dnr K基因中断突变株新次级代谢产物。方法将dnr K基因中插入了阿泊拉霉素抗性基因及"海正"标记片段的中断载体p BSSP-KA导入波赛链霉菌HS062,筛选获得dnr K插入失活的突变株DK55,通过HPLC-MS和NMR对DK55菌株产生的新代谢产物进行结构鉴定。结果 dnr K中断突变株DK55产生了一个新的蒽环类代谢产物,该化合物经结构鉴定为histomodulin,并且其效价远远高于原产物柔红霉素。结论本研究通过基因工程手段获得高产histomodulin菌株,为该化合物的应用研究打下了基础;同时,探讨了工业菌株中dnr K基因敲除后菌株代谢产物变化原因,为进一步提高柔红霉素及其衍生物的产量提供了新的思路。
[Abstract]:Objective to identify Streptomyces oxysporum HS062 (daunorubicin industrial strain). Methods A new secondary metabolite of dnr K gene interruption mutant was inserted into the dnr K gene and the interruption vector of "Haizheng" marker fragment was inserted into the dnr K gene. BSSP-KA was introduced into Streptomyces HS062. Dnr K inserted inactivated mutant DK55 was obtained. The new metabolites produced by DK55 strain were identified by HPLC-MS and NMR. Results A new anthracycline metabolite was produced by dnr K mutant DK55. The compound was identified as histomodulin by structure. The titer of Daunorubicin was much higher than that of daunorubicin. Conclusion the high yield histomodulin strain was obtained by genetic engineering in this study, which laid a foundation for the application of the compound. At the same time, the changes of metabolites after dnr K gene knockout in industrial strains were discussed, which provided a new idea for further improving the yield of daunorubicin and its derivatives.
【作者单位】： 浙江海正药业股份有限公司;
【基金】：台州市企业重点技术创新团队项目(海正药业微生物源抗肿瘤药物研发创新团队)
【分类号】：R379
【正文快照】： 自1963年意大利学者Di Marco等[1]从波赛链霉菌(Streptomyces peucetius)分离获得柔红霉素(daunorubicin,6)以来,国内外学者对波赛链霉菌进行了深入研究,先后分离出多柔比星(doxorubicin,7)[2]、表柔红霉素(epidaunorubicin)[3]、表阿霉素(epirubicin)[3]、洋红霉素(carminomy，

本文编号：1382621