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

• Published in: Science China. Life sciences Vol. 60; no. 9; pp. 992 - 999
• Main Authors: Yin, Shouliang, Wang, Xuefeng, Shi, Mingxin, Yuan, Fang, Wang, Huizhuan, Jia, Xiaole, Sun, Jinliang, Liu, Tiejun, Yang, Keqian, Zhang, Yuxiu, Fan, Keqiang, Li, Zilong
• Format: Journal Article
• Language: English
• Published: Beijing Science China Press 01.09.2017; Springer Nature B.V
• Subjects: Antibiotics; Bacterial Proteins - genetics; Biomedical and Life Sciences; Biosynthetic Pathways - genetics; Drug Resistance, Bacterial - genetics; Gene Expression Regulation, Bacterial - genetics; Genes, Regulator - genetics; Genetic Enhancement; Industrial Microbiology - methods; Life Sciences; Membrane Transport Proteins - genetics; Oxytetracycline; Oxytetracycline - biosynthesis; Research Paper; Self; Streptomyces; Streptomyces rimosus - genetics; Streptomyces rimosus - metabolism; 合作; 土霉素; 抗性基因; 抗生素生产; 过度表达; 重组菌株; 龟裂链霉菌; resistance genes; combinatorial overexpression; oxytetracycline; cluster-situated activator; Streptomyces rimosus
• ISSN: 1674-7305; 1869-1889; 1869-1889
• DOI: 10.1007/s11427-017-9121-4

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.