Improvement of oxytetracycline production mediated via cooperation of resistance genes in Streptomyces rimosus

查看全文 作　　者：Shouliang [1,2]Yin;Xuefeng [3]Wang;Mingxin [1]Shi;Fang [1]Yuan;Huizhuan [3]Wang;Xiaole [3]Jia;Fang [3]Yuan;Jinliang [3]Sun;Tiejun [3]Liu;Keqian [1]Yang;Yuxiu [2]Zhang;Keqiang [1]Fan;Zilong [1]Li

机构地区：[1]State Key Laboratory of Microbial Resources,Institute of Microbiology,Chinese Academy of Sciences;[2]Department of Environmental and Biological Engineering,School of Chemical and Environmental Engineering,China University of Mining and Technology(Beijing);[3]Shengxue Dacheng Pharmaceutical Co.,Ltd;

出　　处：《Science China(Life Sciences)》索引2017年第60卷第9期,共8页

基　　金：supported by funding from Shengxue Dacheng Pharmaceutical Co.,Ltd,National Natural Science Foundation of China(31400034 and 31570031);the Ministry of Science and Technology of China(2013CB734001) 摘　　要：Increasing the self-resistance levels of Streptomyces is an effective strategy to improve the production of antibiotics.To increase the oxytetracycline(OTC) production in Streptomyces rimosus,we investigated the cooperative effect of three co-overexpressing OTC resistance genes:one gene encodes a ribosomal protection protein(otrA) and the other two express efflux proteins(otrB and otrC).Results indicated that combinational overexpression of otrA,otrB,and otrC(MKABC) exerted a synergetic effect.OTC production increased by 179%in the recombinant strain compared with that of the wild-type strain M4018.The resistance level to OTC was increased by approximately two-fold relative to the parental strain,thereby indicating that applying the cooperative effect of self-resistance genes is useful to improve OTC production.Furthermore,the previously identified cluster-situated activator OtcR was overexpressed in MKABC in constructing the recombinant strain MKRABC;such strain can produce OTC of approximately7.49 g L^((-1)),which represents an increase of 19%in comparison with that of the OtcR-overexpressing strain alone.Our work showed that the cooperative overexpression of self-resistance genes is a promising strategy to enhance the antibiotics production in Streptomyces. 关键词：抗生素生产龟裂链霉菌抗性基因土霉素 STREPTOMYCES 过度表达重组菌株合作

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Improvement of oxytetracycline production mediated via cooperation of resistance genes in Streptomyces rimosus

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