Identification of two novel regulatory genes involved in pristinamycin biosynthesis and elucidation of the mechanism for AtrA-p-mediated regulation in Streptomyces pristinaespiralis

Verfasser / Beitragende:
[Wenfang Wang, Jinzhong Tian, Lei Li, Mei Ge, Hong Zhu, Guosong Zheng, He Huang, Lijun Ruan, Weihong Jiang, Yinhua Lu]
Ort, Verlag, Jahr:
2015
Enthalten in:
Applied Microbiology and Biotechnology, 99/17(2015-09-01), 7151-7164
Format:
Artikel (online)
ID: 605502781
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024 7 0 |a 10.1007/s00253-015-6638-6  |2 doi 
035 |a (NATIONALLICENCE)springer-10.1007/s00253-015-6638-6 
245 0 0 |a Identification of two novel regulatory genes involved in pristinamycin biosynthesis and elucidation of the mechanism for AtrA-p-mediated regulation in Streptomyces pristinaespiralis  |h [Elektronische Daten]  |c [Wenfang Wang, Jinzhong Tian, Lei Li, Mei Ge, Hong Zhu, Guosong Zheng, He Huang, Lijun Ruan, Weihong Jiang, Yinhua Lu] 
520 3 |a In this study, using a transposon-based strategy, two novel regulatory genes were identified as being involved in the biosynthesis of both pristinamycin I (PI) and II (PII) in Streptomyces pristinaespiralis, including a TetR-family regulatory gene atrA-p (SSDG_00466) and an orphan histidine kinase gene SSDG_02492. The mechanism by which AtrA-p exerted a positive role in pristinamycin production was elucidated. We showed that deletion of atrA-p resulted in a delayed production of both PI and PII as well as reduced PII production. Transcriptional analysis integrated with electrophoretic mobility shift assays (EMSAs) demonstrated that AtrA-p played a positive role in pristinamycin production by directly activating the transcription of two cluster-situated regulatory genes, spbR and papR5, which encode a γ-butyrolactone receptor protein and a TetR-family repressor, respectively. The precise AtrA-p-binding sites upstream of these two targets were determined, which allowed the identification of a relatively conserved binding motif comprising two 5-nt inverted repeats separated by a variable 5-nt sequence (5′-GGAAT-n5-ATTCC-3′) possibly required for the regulation of AtrA-like regulators in Streptomyces. Base substitutions of the AtrA-p-binding sites on the genome caused similar decreases in spbR and papR5 transcription as those observed in ∆atrA-p. Taken together, herein, a novel mechanism for AtrA-dependent regulation of antibiotic biosynthesis was revealed in S. pristinaespiralis, which is distinct from those of its homologs, AtrA-c from Streptomyces coelicolor, AtrA-g from Streptomyces griseus, and AtrA from Streptomyces roseosporus that perform their effects in antibiotic biosynthesis directly via pathway-specific activator genes or the biosynthetic structural genes. 
540 |a Springer-Verlag Berlin Heidelberg, 2015 
690 7 |a Streptomyces pristinaespiralis  |2 nationallicence 
690 7 |a Pristinamycin  |2 nationallicence 
690 7 |a Regulation  |2 nationallicence 
690 7 |a Transposon  |2 nationallicence 
690 7 |a AtrA  |2 nationallicence 
700 1 |a Wang  |D Wenfang  |u Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200032, Shanghai, People's Republic of China  |4 aut 
700 1 |a Tian  |D Jinzhong  |u Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200032, Shanghai, People's Republic of China  |4 aut 
700 1 |a Li  |D Lei  |u Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200032, Shanghai, People's Republic of China  |4 aut 
700 1 |a Ge  |D Mei  |u Shanghai Laiyi Center for Biopharmaceuticals R&D, 201203, Shanghai, People's Republic of China  |4 aut 
700 1 |a Zhu  |D Hong  |u Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200032, Shanghai, People's Republic of China  |4 aut 
700 1 |a Zheng  |D Guosong  |u Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200032, Shanghai, People's Republic of China  |4 aut 
700 1 |a Huang  |D He  |u Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200032, Shanghai, People's Republic of China  |4 aut 
700 1 |a Ruan  |D Lijun  |u Shanghai Laiyi Center for Biopharmaceuticals R&D, 201203, Shanghai, People's Republic of China  |4 aut 
700 1 |a Jiang  |D Weihong  |u Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200032, Shanghai, People's Republic of China  |4 aut 
700 1 |a Lu  |D Yinhua  |u Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200032, Shanghai, People's Republic of China  |4 aut 
773 0 |t Applied Microbiology and Biotechnology  |d Springer Berlin Heidelberg  |g 99/17(2015-09-01), 7151-7164  |x 0175-7598  |q 99:17<7151  |1 2015  |2 99  |o 253 
856 4 0 |u https://doi.org/10.1007/s00253-015-6638-6  |q text/html  |z Onlinezugriff via DOI 
898 |a BK010053  |b XK010053  |c XK010000 
900 7 |a Metadata rights reserved  |b Springer special CC-BY-NC licence  |2 nationallicence 
908 |D 1  |a research-article  |2 jats 
949 |B NATIONALLICENCE  |F NATIONALLICENCE  |b NL-springer 
950 |B NATIONALLICENCE  |P 856  |E 40  |u https://doi.org/10.1007/s00253-015-6638-6  |q text/html  |z Onlinezugriff via DOI 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Wang  |D Wenfang  |u Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200032, Shanghai, People's Republic of China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Tian  |D Jinzhong  |u Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200032, Shanghai, People's Republic of China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Li  |D Lei  |u Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200032, Shanghai, People's Republic of China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Ge  |D Mei  |u Shanghai Laiyi Center for Biopharmaceuticals R&D, 201203, Shanghai, People's Republic of China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Zhu  |D Hong  |u Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200032, Shanghai, People's Republic of China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Zheng  |D Guosong  |u Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200032, Shanghai, People's Republic of China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Huang  |D He  |u Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200032, Shanghai, People's Republic of China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Ruan  |D Lijun  |u Shanghai Laiyi Center for Biopharmaceuticals R&D, 201203, Shanghai, People's Republic of China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Jiang  |D Weihong  |u Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200032, Shanghai, People's Republic of China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Lu  |D Yinhua  |u Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200032, Shanghai, People's Republic of China  |4 aut 
950 |B NATIONALLICENCE  |P 773  |E 0-  |t Applied Microbiology and Biotechnology  |d Springer Berlin Heidelberg  |g 99/17(2015-09-01), 7151-7164  |x 0175-7598  |q 99:17<7151  |1 2015  |2 99  |o 253