文献类型：期刊文献

英文题名：Developmental regulator RamRsl controls both morphological development and lincomycin biosynthesis in Streptomyces lincolnensis

作者：Wang, Ruida[1];Cao, Yuan[1];Kong, Fanjing[1];Hou, Bingbing[1,2];Zhao, Jiaqi[1];Kang, Yajing[1];Ye, Jiang[1,2];Wu, Haizhen[1,2];Zhang, Huizhan[1,2]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai, Peoples R China;[2]East China Univ Sci & Technol, Dept Appl Biol, Shanghai 200237, Peoples R China

年份：2022

卷号：133

期号：2

起止页码：400

外文期刊名：JOURNAL OF APPLIED MICROBIOLOGY

收录：;EI(收录号：20231713961135);WOS:【SCI-EXPANDED(收录号:WOS:000783285300001)】；

基金：Ministry of Science and Technology of the People's Republic of China, Grant/Award Number: 2019YFC0312500; National Natural Science Foundation of China, Grant/Award Number: 31900059; Postdoctoral Science Foundation of China, Grant/Award Number: 2019M650079; Research Program of State Key Laboratory of Bioreactor Engineering

语种：英文

外文关键词：lincomycin biosynthesis; morphology; RamR; Streptomyces lincolnensis; transcriptional regulation

摘要：Aims Assessing the role of ramR(sl), a gene absent in a lincomycin over-producing strain, in the regulation of morphological development and lincomycin biosynthesis in Streptomyces lincolnensis. Methods and Results The gene ramR(sl) was deleted from the wild-type strain NRRL 2936 and the Delta ramR mutant strain was characterized by a slower growth rate and a delayed morphological differentiation compared to the original strain NRRL 2936. Furthermore, the Delta ramR produced 2.6-fold more lincomycin than the original strain, and consistently the level of expression of all lincomycin cluster located genes was enhanced at 48 and 96 h in the Delta ramR. Complementation of Delta ramR with an intact copy of ramR(sl) restored all wild-type features, whereas the over-expression of ramR(sl) led to a reduction of 33% of the lincomycin yield. Furthermore, the level of expression of glnR, bldA and SLCG_2919, three of known lincomycin biosynthesis regulators, was lower in the Delta ramR than in the original strain at the early stage of fermentation and we demonstrated, using electrophoretic mobility shift assay and XylE reporter assay, that glnR is a novel direct target of RamR. Conclusions Altogether, these results indicated that, beyond promoting the morphological development, RamR regulates negatively lincomycin biosynthesis and positively the expression of the nitrogen regulator GlnR. Significance and Impact of the Study We demonstrated that RamR plays a negative role in the regulation of lincomycin biosynthesis in S. lincolnensis. Interestingly, the deletion of this gene in other antibiotic-producing Streptomyces strains might also increase their antibiotic-producing abilities.