本文關(guān)鍵詞：波賽鏈霉菌dnrK基因中斷突變株代謝產(chǎn)物鑒定　出處：《中國抗生素雜志》2015年11期 　論文類型：期刊論文

  更多相關(guān)文章： 波賽鏈霉菌 dnrK Histomodulin 基因中斷

【摘要】：目的鑒定波賽鏈霉菌HS062(柔紅霉素工業(yè)菌株)dnr K基因中斷突變株新次級代謝產(chǎn)物。方法將dnr K基因中插入了阿泊拉霉素抗性基因及"海正"標(biāo)記片段的中斷載體p BSSP-KA導(dǎo)入波賽鏈霉菌HS062,篩選獲得dnr K插入失活的突變株DK55,通過HPLC-MS和NMR對DK55菌株產(chǎn)生的新代謝產(chǎn)物進(jìn)行結(jié)構(gòu)鑒定。結(jié)果 dnr K中斷突變株DK55產(chǎn)生了一個新的蒽環(huán)類代謝產(chǎn)物,該化合物經(jīng)結(jié)構(gòu)鑒定為histomodulin,并且其效價遠(yuǎn)遠(yuǎn)高于原產(chǎn)物柔紅霉素。結(jié)論本研究通過基因工程手段獲得高產(chǎn)histomodulin菌株,為該化合物的應(yīng)用研究打下了基礎(chǔ);同時,探討了工業(yè)菌株中dnr K基因敲除后菌株代謝產(chǎn)物變化原因,為進(jìn)一步提高柔紅霉素及其衍生物的產(chǎn)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.
【作者單位】： 浙江海正藥業(yè)股份有限公司;
【基金】：臺州市企業(yè)重點技術(shù)創(chuàng)新團隊項目(海正藥業(yè)微生物源抗腫瘤藥物研發(fā)創(chuàng)新團隊)
【分類號】：R379
【正文快照】： 自1963年意大利學(xué)者Di Marco等[1]從波賽鏈霉菌(Streptomyces peucetius)分離獲得柔紅霉素(daunorubicin,6)以來,國內(nèi)外學(xué)者對波賽鏈霉菌進(jìn)行了深入研究,先后分離出多柔比星(doxorubicin,7)[2]、表柔紅霉素(epidaunorubicin)[3]、表阿霉素(epirubicin)[3]、洋紅霉素(carminomy，

本文編號：1382621