Role of <it>sgcR3 </it>in positive regulation of enediyne antibiotic C-1027 production of <it>Streptomyces globisporus </it>C-1027

<p>Abstract</p> <p>Background</p> <p>C-1027, produced by <it>Streptomyces globisporus </it>C-1027, is one of the most potent antitumoral agents. The biosynthetic gene cluster of C-1027, previously cloned and sequenced, contains at least three putative regula...

Full description

Bibliographic Details
Main Authors: Jiang Wei, Bao Yi, Cui Zhihui, Wang Songmei, Zhang Yanjuan, Hu Yunfeng, Wang Lifei, Hong Bin
Format: Article
Language:English
Published: BMC 2009-01-01
Series:BMC Microbiology
Online Access:http://www.biomedcentral.com/1471-2180/9/14
_version_ 1811313532506996736
author Jiang Wei
Bao Yi
Cui Zhihui
Wang Songmei
Zhang Yanjuan
Hu Yunfeng
Wang Lifei
Hong Bin
author_facet Jiang Wei
Bao Yi
Cui Zhihui
Wang Songmei
Zhang Yanjuan
Hu Yunfeng
Wang Lifei
Hong Bin
author_sort Jiang Wei
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>C-1027, produced by <it>Streptomyces globisporus </it>C-1027, is one of the most potent antitumoral agents. The biosynthetic gene cluster of C-1027, previously cloned and sequenced, contains at least three putative regulatory genes, i.e. <it>sgcR1</it>, <it>sgcR2 </it>and <it>sgcR3</it>. The predicted gene products of these genes share sequence similarities to StrR, regulators of AraC/XylS family and TylR. The purpose of this study was to investigate the role of <it>sgcR3 </it>in C-1027 biosynthesis.</p> <p>Results</p> <p>Overexpression of <it>sgcR3 </it>in <it>S. globisporus </it>C-1027 resulted in a 30–40% increase in C-1027 production. Consistent with this, disruption of <it>sgcR3 </it>abolished C-1027 production. Complementation of the <it>sgcR3</it>-disrupted strain R3KO with intact <it>sgcR3 </it>gene could restore C-1027 production. The results from real time RT-PCR analysis in R3KO mutant and wild type strain indicated that not only transcripts of biosynthetic structural genes such as <it>sgcA1 </it>and <it>sgcC4</it>, but also putative regulatory genes, <it>sgcR1 </it>and <it>sgcR2</it>, were significantly decreased in R3KO mutant. The cross-complementation studies showed that <it>sgcR1R2 </it>could functionally complement <it>sgcR3 </it>disruption <it>in trans</it>. Purified N-terminal His<sub>10</sub>-tagged SgcR3 showed specific DNA-binding activity to the promoter region of <it>sgcR1R2</it>.</p> <p>Conclusion</p> <p>The role of SgcR3 has been proved to be a positive regulator of C-1027 biosynthesis in <it>S. globisporus </it>C-1027. SgcR3 occupies a higher level than SgcR1 and SgcR2 in the regulatory hierarchy that controls C-1027 production and activates the transcription of <it>sgcR1 </it>and <it>sgcR2 </it>by binding directly to the promoter region of <it>sgcR1R2</it>.</p>
first_indexed 2024-04-13T10:55:29Z
format Article
id doaj.art-3bb74199d3c74a04bd0f8015c9dbc814
institution Directory Open Access Journal
issn 1471-2180
language English
last_indexed 2024-04-13T10:55:29Z
publishDate 2009-01-01
publisher BMC
record_format Article
series BMC Microbiology
spelling doaj.art-3bb74199d3c74a04bd0f8015c9dbc8142022-12-22T02:49:32ZengBMCBMC Microbiology1471-21802009-01-01911410.1186/1471-2180-9-14Role of <it>sgcR3 </it>in positive regulation of enediyne antibiotic C-1027 production of <it>Streptomyces globisporus </it>C-1027Jiang WeiBao YiCui ZhihuiWang SongmeiZhang YanjuanHu YunfengWang LifeiHong Bin<p>Abstract</p> <p>Background</p> <p>C-1027, produced by <it>Streptomyces globisporus </it>C-1027, is one of the most potent antitumoral agents. The biosynthetic gene cluster of C-1027, previously cloned and sequenced, contains at least three putative regulatory genes, i.e. <it>sgcR1</it>, <it>sgcR2 </it>and <it>sgcR3</it>. The predicted gene products of these genes share sequence similarities to StrR, regulators of AraC/XylS family and TylR. The purpose of this study was to investigate the role of <it>sgcR3 </it>in C-1027 biosynthesis.</p> <p>Results</p> <p>Overexpression of <it>sgcR3 </it>in <it>S. globisporus </it>C-1027 resulted in a 30–40% increase in C-1027 production. Consistent with this, disruption of <it>sgcR3 </it>abolished C-1027 production. Complementation of the <it>sgcR3</it>-disrupted strain R3KO with intact <it>sgcR3 </it>gene could restore C-1027 production. The results from real time RT-PCR analysis in R3KO mutant and wild type strain indicated that not only transcripts of biosynthetic structural genes such as <it>sgcA1 </it>and <it>sgcC4</it>, but also putative regulatory genes, <it>sgcR1 </it>and <it>sgcR2</it>, were significantly decreased in R3KO mutant. The cross-complementation studies showed that <it>sgcR1R2 </it>could functionally complement <it>sgcR3 </it>disruption <it>in trans</it>. Purified N-terminal His<sub>10</sub>-tagged SgcR3 showed specific DNA-binding activity to the promoter region of <it>sgcR1R2</it>.</p> <p>Conclusion</p> <p>The role of SgcR3 has been proved to be a positive regulator of C-1027 biosynthesis in <it>S. globisporus </it>C-1027. SgcR3 occupies a higher level than SgcR1 and SgcR2 in the regulatory hierarchy that controls C-1027 production and activates the transcription of <it>sgcR1 </it>and <it>sgcR2 </it>by binding directly to the promoter region of <it>sgcR1R2</it>.</p>http://www.biomedcentral.com/1471-2180/9/14
spellingShingle Jiang Wei
Bao Yi
Cui Zhihui
Wang Songmei
Zhang Yanjuan
Hu Yunfeng
Wang Lifei
Hong Bin
Role of <it>sgcR3 </it>in positive regulation of enediyne antibiotic C-1027 production of <it>Streptomyces globisporus </it>C-1027
BMC Microbiology
title Role of <it>sgcR3 </it>in positive regulation of enediyne antibiotic C-1027 production of <it>Streptomyces globisporus </it>C-1027
title_full Role of <it>sgcR3 </it>in positive regulation of enediyne antibiotic C-1027 production of <it>Streptomyces globisporus </it>C-1027
title_fullStr Role of <it>sgcR3 </it>in positive regulation of enediyne antibiotic C-1027 production of <it>Streptomyces globisporus </it>C-1027
title_full_unstemmed Role of <it>sgcR3 </it>in positive regulation of enediyne antibiotic C-1027 production of <it>Streptomyces globisporus </it>C-1027
title_short Role of <it>sgcR3 </it>in positive regulation of enediyne antibiotic C-1027 production of <it>Streptomyces globisporus </it>C-1027
title_sort role of it sgcr3 it in positive regulation of enediyne antibiotic c 1027 production of it streptomyces globisporus it c 1027
url http://www.biomedcentral.com/1471-2180/9/14
work_keys_str_mv AT jiangwei roleofitsgcr3itinpositiveregulationofenediyneantibioticc1027productionofitstreptomycesglobisporusitc1027
AT baoyi roleofitsgcr3itinpositiveregulationofenediyneantibioticc1027productionofitstreptomycesglobisporusitc1027
AT cuizhihui roleofitsgcr3itinpositiveregulationofenediyneantibioticc1027productionofitstreptomycesglobisporusitc1027
AT wangsongmei roleofitsgcr3itinpositiveregulationofenediyneantibioticc1027productionofitstreptomycesglobisporusitc1027
AT zhangyanjuan roleofitsgcr3itinpositiveregulationofenediyneantibioticc1027productionofitstreptomycesglobisporusitc1027
AT huyunfeng roleofitsgcr3itinpositiveregulationofenediyneantibioticc1027productionofitstreptomycesglobisporusitc1027
AT wanglifei roleofitsgcr3itinpositiveregulationofenediyneantibioticc1027productionofitstreptomycesglobisporusitc1027
AT hongbin roleofitsgcr3itinpositiveregulationofenediyneantibioticc1027productionofitstreptomycesglobisporusitc1027