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CtcS, a MarR family regulator, regulates chlortetracycline biosynthesis

BACKGROUND: Chlortetracycline (CTC) is one of the commercially important tetracyclines (TCs) family product and is mainly produced by Streptomyces. CTC is still in a great demand due to its broad-spectrum activity against pathogens. Engineering transcriptional control allows the cell to allocate its...

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Autores principales: Kong, Lingxin, Liu, Jia, Zheng, Xiaoqing, Deng, Zixin, You, Delin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6905112/
https://www.ncbi.nlm.nih.gov/pubmed/31823730
http://dx.doi.org/10.1186/s12866-019-1670-9
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author Kong, Lingxin
Liu, Jia
Zheng, Xiaoqing
Deng, Zixin
You, Delin
author_facet Kong, Lingxin
Liu, Jia
Zheng, Xiaoqing
Deng, Zixin
You, Delin
author_sort Kong, Lingxin
collection PubMed
description BACKGROUND: Chlortetracycline (CTC) is one of the commercially important tetracyclines (TCs) family product and is mainly produced by Streptomyces. CTC is still in a great demand due to its broad-spectrum activity against pathogens. Engineering transcriptional control allows the cell to allocate its valuable resources towards protein production and provides an important method for the build-up of desired metabolites. Despite extensive efforts concerning transcriptional regulation for increasing the productivities of TCs, the regulatory mechanisms of the CTC biosynthesis remain poorly understood. RESULTS: In this study, the possible regulatory function of CtcS, a potential member of MarR (multiple antibiotic resistance regulator) family of transcriptional regulators in S. aureofaciens F3, was demonstrated. Knockdown of ctcS altered the transcription of several biosynthesis-related genes and reduced the production of tetracycline (TC) and CTC, without obvious effect on morphological differentiation and cell growth. Especially, CtcS directly repressed the transcription of the adjacent divergent gene ctcR (which encodes a putative TC resistance efflux protein). A CtcS-binding site was identified within the promoter region of ctcR by DNase I footprinting and an inverted repeat (5′-CTTGTC-3′) composed of two 6-nt half sites in the protected region was found. Moreover, both CTC and TC could attenuate the binding activity of CtcS with target DNA. CONCLUSION: ctcS regulated the production of TC and CTC in S. aureofaciens F3 and the overexpression of it could be used as a simple approach for the construction of engineering strain with higher productivity. Meanwhile, CtcS was characterized as a TC- and CTC-responsive MarR family regulator. This study provides a previously unrecognized function of CtcS and will benefit the research on the regulatory machinery of the MarR family regulators.
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spelling pubmed-69051122019-12-19 CtcS, a MarR family regulator, regulates chlortetracycline biosynthesis Kong, Lingxin Liu, Jia Zheng, Xiaoqing Deng, Zixin You, Delin BMC Microbiol Research Article BACKGROUND: Chlortetracycline (CTC) is one of the commercially important tetracyclines (TCs) family product and is mainly produced by Streptomyces. CTC is still in a great demand due to its broad-spectrum activity against pathogens. Engineering transcriptional control allows the cell to allocate its valuable resources towards protein production and provides an important method for the build-up of desired metabolites. Despite extensive efforts concerning transcriptional regulation for increasing the productivities of TCs, the regulatory mechanisms of the CTC biosynthesis remain poorly understood. RESULTS: In this study, the possible regulatory function of CtcS, a potential member of MarR (multiple antibiotic resistance regulator) family of transcriptional regulators in S. aureofaciens F3, was demonstrated. Knockdown of ctcS altered the transcription of several biosynthesis-related genes and reduced the production of tetracycline (TC) and CTC, without obvious effect on morphological differentiation and cell growth. Especially, CtcS directly repressed the transcription of the adjacent divergent gene ctcR (which encodes a putative TC resistance efflux protein). A CtcS-binding site was identified within the promoter region of ctcR by DNase I footprinting and an inverted repeat (5′-CTTGTC-3′) composed of two 6-nt half sites in the protected region was found. Moreover, both CTC and TC could attenuate the binding activity of CtcS with target DNA. CONCLUSION: ctcS regulated the production of TC and CTC in S. aureofaciens F3 and the overexpression of it could be used as a simple approach for the construction of engineering strain with higher productivity. Meanwhile, CtcS was characterized as a TC- and CTC-responsive MarR family regulator. This study provides a previously unrecognized function of CtcS and will benefit the research on the regulatory machinery of the MarR family regulators. BioMed Central 2019-12-10 /pmc/articles/PMC6905112/ /pubmed/31823730 http://dx.doi.org/10.1186/s12866-019-1670-9 Text en © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Kong, Lingxin
Liu, Jia
Zheng, Xiaoqing
Deng, Zixin
You, Delin
CtcS, a MarR family regulator, regulates chlortetracycline biosynthesis
title CtcS, a MarR family regulator, regulates chlortetracycline biosynthesis
title_full CtcS, a MarR family regulator, regulates chlortetracycline biosynthesis
title_fullStr CtcS, a MarR family regulator, regulates chlortetracycline biosynthesis
title_full_unstemmed CtcS, a MarR family regulator, regulates chlortetracycline biosynthesis
title_short CtcS, a MarR family regulator, regulates chlortetracycline biosynthesis
title_sort ctcs, a marr family regulator, regulates chlortetracycline biosynthesis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6905112/
https://www.ncbi.nlm.nih.gov/pubmed/31823730
http://dx.doi.org/10.1186/s12866-019-1670-9
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