caa a22 4500 606212175 CHVBK 20210128101041.0 cr unu---uuuuu 210128e20150901xx s 000 0 eng 10.1007/s10295-015-1660-3 doi (NATIONALLICENCE)springer-10.1007/s10295-015-1660-3 Functional manipulations of the tetramycin positive regulatory gene ttmRIV to enhance the production of tetramycin A and nystatin A1 in Streptomyces ahygroscopicus [Elektronische Daten] [Hao Cui, Xianpu Ni, Wei Shao, Jian Su, Jiaqi Su, Jun Ren, Huanzhang Xia] A putative regulatory gene ttmRIV located in the tetramycin biosynthetic gene cluster was found in Streptomyces ahygroscopicus. In-frame deletion of ttmRIV led to abolishment of tetramycin and significant enhancement of nystatin A1, whose production reached 2.1-fold of the H42 parental strain. Gene complementation by an integrative plasmid carrying ttmRIV restored tetramycin biosynthesis revealed that ttmRIV was indispensable to tetramycin biosynthesis. Gene expression analysis of the H42 strain and its mutant strain ΔttmRIV via reverse transcriptase-PCR of the tetramycin gene cluster demonstrated that the expression levels of most biosynthetic genes were reduced in ΔttmRIV. Results of electrophoretic mobility shift assays showed that TtmRIV bound the putative promoters of several genes in the tetramycin pathway. Thus, TtmRIV is a pathway-specific positive regulator activating the transcription of the tetramycin gene cluster in S. ahygroscopicus. Providing an additional copy of ttmRIV under the control of the ermEp* promoter in the H42 strain boosted tetramycin A production to 3.3-fold. Society for Industrial Microbiology and Biotechnology, 2015 PAS-LuxR nationallicence Regulator nationallicence Streptomyces nationallicence Tetramycin nationallicence Nystatin A1 nationallicence Cui Hao School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical Univerisity, Shenhe District, Wenhua Road 103, 110016, Shenyang, Liaoning, People's Republic of China aut Ni Xianpu School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical Univerisity, Shenhe District, Wenhua Road 103, 110016, Shenyang, Liaoning, People's Republic of China aut Shao Wei School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical Univerisity, Shenhe District, Wenhua Road 103, 110016, Shenyang, Liaoning, People's Republic of China aut Su Jian School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical Univerisity, Shenhe District, Wenhua Road 103, 110016, Shenyang, Liaoning, People's Republic of China aut Su Jiaqi School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical Univerisity, Shenhe District, Wenhua Road 103, 110016, Shenyang, Liaoning, People's Republic of China aut Ren Jun School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical Univerisity, Shenhe District, Wenhua Road 103, 110016, Shenyang, Liaoning, People's Republic of China aut Xia Huanzhang School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical Univerisity, Shenhe District, Wenhua Road 103, 110016, Shenyang, Liaoning, People's Republic of China aut Journal of Industrial Microbiology & Biotechnology Springer Berlin Heidelberg 42/9(2015-09-01), 1273-1282 1367-5435 42:9<1273 2015 42 10295 https://doi.org/10.1007/s10295-015-1660-3 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10295-015-1660-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Cui Hao School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical Univerisity, Shenhe District, Wenhua Road 103, 110016, Shenyang, Liaoning, People's Republic of China aut NATIONALLICENCE 700 1- Ni Xianpu School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical Univerisity, Shenhe District, Wenhua Road 103, 110016, Shenyang, Liaoning, People's Republic of China aut NATIONALLICENCE 700 1- Shao Wei School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical Univerisity, Shenhe District, Wenhua Road 103, 110016, Shenyang, Liaoning, People's Republic of China aut NATIONALLICENCE 700 1- Su Jian School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical Univerisity, Shenhe District, Wenhua Road 103, 110016, Shenyang, Liaoning, People's Republic of China aut NATIONALLICENCE 700 1- Su Jiaqi School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical Univerisity, Shenhe District, Wenhua Road 103, 110016, Shenyang, Liaoning, People's Republic of China aut NATIONALLICENCE 700 1- Ren Jun School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical Univerisity, Shenhe District, Wenhua Road 103, 110016, Shenyang, Liaoning, People's Republic of China aut NATIONALLICENCE 700 1- Xia Huanzhang School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical Univerisity, Shenhe District, Wenhua Road 103, 110016, Shenyang, Liaoning, People's Republic of China aut NATIONALLICENCE 773 0- Journal of Industrial Microbiology & Biotechnology Springer Berlin Heidelberg 42/9(2015-09-01), 1273-1282 1367-5435 42:9<1273 2015 42 10295