Initiation of actinorhodin export in Streptomyces coelicolor
Many microorganisms produce molecules having antibiotic activity and expel them into the environment, presumably enhancing their ability to compete with their neighbours. Given that these molecules are often toxic to the producer, mechanisms must exist to ensure that the assembly of the export appar...
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| Veröffentlicht in: | Molecular microbiology 2007-02, Vol.63 (4), p.951-961 |
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| creator | Tahlan, Kapil Ahn, Sang Kyun Sing, Anson Bodnaruk, Tetyana D Willems, Andrew R Davidson, Alan R Nodwell, Justin R |
| description | Many microorganisms produce molecules having antibiotic activity and expel them into the environment, presumably enhancing their ability to compete with their neighbours. Given that these molecules are often toxic to the producer, mechanisms must exist to ensure that the assembly of the export apparatus accompanies or precedes biosynthesis. Streptomyces coelicolor produces the polyketide antibiotic actinorhodin in a multistep pathway involving enzymes encoded by genes that are clustered together. Embedded within the cluster are genes for actinorhodin export, two of which, actR and actA resemble the classic tetR and tetA repressor/efflux pump-encoding gene pairs that confer resistance to tetracycline. Like TetR, which represses tetA, ActR is a repressor of actA. We have identified several molecules that can relieve repression by ActR. Importantly (S)-DNPA (an intermediate in the actinorhodin biosynthetic pathway) and kalafungin (a molecule related to the intermediate dihydrokalafungin), are especially potent ActR ligands. This suggests that along with the mature antibiotic(s), intermediates in the biosynthetic pathway might activate expression of the export genes thereby coupling export to biosynthesis. We suggest that this could be a common feature in the production of many bioactive natural products. |
| doi_str_mv | 10.1111/j.1365-2958.2006.05559.x |
| format | Article |
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Given that these molecules are often toxic to the producer, mechanisms must exist to ensure that the assembly of the export apparatus accompanies or precedes biosynthesis. Streptomyces coelicolor produces the polyketide antibiotic actinorhodin in a multistep pathway involving enzymes encoded by genes that are clustered together. Embedded within the cluster are genes for actinorhodin export, two of which, actR and actA resemble the classic tetR and tetA repressor/efflux pump-encoding gene pairs that confer resistance to tetracycline. Like TetR, which represses tetA, ActR is a repressor of actA. We have identified several molecules that can relieve repression by ActR. Importantly (S)-DNPA (an intermediate in the actinorhodin biosynthetic pathway) and kalafungin (a molecule related to the intermediate dihydrokalafungin), are especially potent ActR ligands. This suggests that along with the mature antibiotic(s), intermediates in the biosynthetic pathway might activate expression of the export genes thereby coupling export to biosynthesis. We suggest that this could be a common feature in the production of many bioactive natural products.</description><identifier>ISSN: 0950-382X</identifier><identifier>EISSN: 1365-2958</identifier><identifier>DOI: 10.1111/j.1365-2958.2006.05559.x</identifier><identifier>PMID: 17338074</identifier><language>eng</language><publisher>Oxford, UK: Oxford, UK : Blackwell Publishing Ltd</publisher><subject>Anthraquinones - metabolism ; Anti-Bacterial Agents - metabolism ; Antibiotics ; Bacteria ; Bacterial Proteins - genetics ; Bacterial Proteins - metabolism ; Bacteriology ; Biological and medical sciences ; Biological Transport ; Biosensing Techniques ; Chemical synthesis ; DNA, Bacterial - metabolism ; Fundamental and applied biological sciences. Psychology ; Gene expression ; Gene Expression Regulation, Bacterial - drug effects ; Ligands ; Microbiology ; Miscellaneous ; Molecular biology ; Multigene Family ; Mutation ; Naphthalenes - metabolism ; Naphthoquinones - metabolism ; Pyrans - metabolism ; Repressor Proteins - drug effects ; Repressor Proteins - genetics ; Repressor Proteins - metabolism ; Streptomyces coelicolor ; Streptomyces coelicolor - drug effects ; Streptomyces coelicolor - genetics ; Streptomyces coelicolor - metabolism ; Tetracycline - pharmacology</subject><ispartof>Molecular microbiology, 2007-02, Vol.63 (4), p.951-961</ispartof><rights>2007 INIST-CNRS</rights><rights>Copyright Blackwell Publishing Feb 2007</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5299-16a790a6cd8051e6863eb727fa9fa2a9fd655e25774d5c6049f3aed5e6611abe3</citedby><cites>FETCH-LOGICAL-c5299-16a790a6cd8051e6863eb727fa9fa2a9fd655e25774d5c6049f3aed5e6611abe3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1365-2958.2006.05559.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1365-2958.2006.05559.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,1427,27903,27904,45553,45554,46387,46811</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18487527$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17338074$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tahlan, Kapil</creatorcontrib><creatorcontrib>Ahn, Sang Kyun</creatorcontrib><creatorcontrib>Sing, Anson</creatorcontrib><creatorcontrib>Bodnaruk, Tetyana D</creatorcontrib><creatorcontrib>Willems, Andrew R</creatorcontrib><creatorcontrib>Davidson, Alan R</creatorcontrib><creatorcontrib>Nodwell, Justin R</creatorcontrib><title>Initiation of actinorhodin export in Streptomyces coelicolor</title><title>Molecular microbiology</title><addtitle>Mol Microbiol</addtitle><description>Many microorganisms produce molecules having antibiotic activity and expel them into the environment, presumably enhancing their ability to compete with their neighbours. Given that these molecules are often toxic to the producer, mechanisms must exist to ensure that the assembly of the export apparatus accompanies or precedes biosynthesis. Streptomyces coelicolor produces the polyketide antibiotic actinorhodin in a multistep pathway involving enzymes encoded by genes that are clustered together. Embedded within the cluster are genes for actinorhodin export, two of which, actR and actA resemble the classic tetR and tetA repressor/efflux pump-encoding gene pairs that confer resistance to tetracycline. Like TetR, which represses tetA, ActR is a repressor of actA. We have identified several molecules that can relieve repression by ActR. Importantly (S)-DNPA (an intermediate in the actinorhodin biosynthetic pathway) and kalafungin (a molecule related to the intermediate dihydrokalafungin), are especially potent ActR ligands. This suggests that along with the mature antibiotic(s), intermediates in the biosynthetic pathway might activate expression of the export genes thereby coupling export to biosynthesis. We suggest that this could be a common feature in the production of many bioactive natural products.</description><subject>Anthraquinones - metabolism</subject><subject>Anti-Bacterial Agents - metabolism</subject><subject>Antibiotics</subject><subject>Bacteria</subject><subject>Bacterial Proteins - genetics</subject><subject>Bacterial Proteins - metabolism</subject><subject>Bacteriology</subject><subject>Biological and medical sciences</subject><subject>Biological Transport</subject><subject>Biosensing Techniques</subject><subject>Chemical synthesis</subject><subject>DNA, Bacterial - metabolism</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Bacterial - drug effects</subject><subject>Ligands</subject><subject>Microbiology</subject><subject>Miscellaneous</subject><subject>Molecular biology</subject><subject>Multigene Family</subject><subject>Mutation</subject><subject>Naphthalenes - metabolism</subject><subject>Naphthoquinones - metabolism</subject><subject>Pyrans - metabolism</subject><subject>Repressor Proteins - drug effects</subject><subject>Repressor Proteins - genetics</subject><subject>Repressor Proteins - metabolism</subject><subject>Streptomyces coelicolor</subject><subject>Streptomyces coelicolor - drug effects</subject><subject>Streptomyces coelicolor - genetics</subject><subject>Streptomyces coelicolor - metabolism</subject><subject>Tetracycline - pharmacology</subject><issn>0950-382X</issn><issn>1365-2958</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkV1rFDEUhoNY7Fr9CzoIejfTk2TyBXohxY-Fll7UgnchmzmjWWYnazKLu__ejLtY8Kq5SA7keU8OTwipKDS0rMt1Q7kUNTNCNwxANiCEMM3-CVn8u3hKFmAE1Fyz7-fkec5rAMpB8mfknCrONah2Qd4vxzAFN4U4VrGvnJ_CGNPP2IWxwv02pqkq1d2UcDvFzcFjrnzEIfg4xPSCnPVuyPjydF6Q-8-fvl19ra9vvyyvPl7XXjBjaiqdMuCk7zQIilJLjivFVO9M71jZOikEMqFU2wkvoTU9d9gJlJJSt0J-Qd4d-25T_LXDPNlNyB6HwY0Yd9kyaAWXoAv45j9wHXdpLLNZaqTgAC0rkD5CPsWcE_Z2m8LGpYOlYGe9dm1ni3a2aGe99q9euy_RV6f-u9UGu4fgyWcB3p4Al70b-uRGH_IDp1utBFOF-3DkfocBD48ewN7cLOeq5F8f872L1v1I5Y37Ozb_7zxF23L-B3QwnmI</recordid><startdate>200702</startdate><enddate>200702</enddate><creator>Tahlan, Kapil</creator><creator>Ahn, Sang Kyun</creator><creator>Sing, Anson</creator><creator>Bodnaruk, Tetyana D</creator><creator>Willems, Andrew R</creator><creator>Davidson, Alan R</creator><creator>Nodwell, Justin R</creator><general>Oxford, UK : Blackwell Publishing Ltd</general><general>Blackwell Publishing Ltd</general><general>Blackwell Science</general><scope>FBQ</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7T7</scope></search><sort><creationdate>200702</creationdate><title>Initiation of actinorhodin export in Streptomyces coelicolor</title><author>Tahlan, Kapil ; Ahn, Sang Kyun ; Sing, Anson ; Bodnaruk, Tetyana D ; Willems, Andrew R ; Davidson, Alan R ; Nodwell, Justin R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5299-16a790a6cd8051e6863eb727fa9fa2a9fd655e25774d5c6049f3aed5e6611abe3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Anthraquinones - metabolism</topic><topic>Anti-Bacterial Agents - metabolism</topic><topic>Antibiotics</topic><topic>Bacteria</topic><topic>Bacterial Proteins - genetics</topic><topic>Bacterial Proteins - metabolism</topic><topic>Bacteriology</topic><topic>Biological and medical sciences</topic><topic>Biological Transport</topic><topic>Biosensing Techniques</topic><topic>Chemical synthesis</topic><topic>DNA, Bacterial - metabolism</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Bacterial - drug effects</topic><topic>Ligands</topic><topic>Microbiology</topic><topic>Miscellaneous</topic><topic>Molecular biology</topic><topic>Multigene Family</topic><topic>Mutation</topic><topic>Naphthalenes - metabolism</topic><topic>Naphthoquinones - metabolism</topic><topic>Pyrans - metabolism</topic><topic>Repressor Proteins - drug effects</topic><topic>Repressor Proteins - genetics</topic><topic>Repressor Proteins - metabolism</topic><topic>Streptomyces coelicolor</topic><topic>Streptomyces coelicolor - drug effects</topic><topic>Streptomyces coelicolor - genetics</topic><topic>Streptomyces coelicolor - metabolism</topic><topic>Tetracycline - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tahlan, Kapil</creatorcontrib><creatorcontrib>Ahn, Sang Kyun</creatorcontrib><creatorcontrib>Sing, Anson</creatorcontrib><creatorcontrib>Bodnaruk, Tetyana D</creatorcontrib><creatorcontrib>Willems, Andrew R</creatorcontrib><creatorcontrib>Davidson, Alan R</creatorcontrib><creatorcontrib>Nodwell, Justin R</creatorcontrib><collection>AGRIS</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><jtitle>Molecular microbiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tahlan, Kapil</au><au>Ahn, Sang Kyun</au><au>Sing, Anson</au><au>Bodnaruk, Tetyana D</au><au>Willems, Andrew R</au><au>Davidson, Alan R</au><au>Nodwell, Justin R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Initiation of actinorhodin export in Streptomyces coelicolor</atitle><jtitle>Molecular microbiology</jtitle><addtitle>Mol Microbiol</addtitle><date>2007-02</date><risdate>2007</risdate><volume>63</volume><issue>4</issue><spage>951</spage><epage>961</epage><pages>951-961</pages><issn>0950-382X</issn><eissn>1365-2958</eissn><abstract>Many microorganisms produce molecules having antibiotic activity and expel them into the environment, presumably enhancing their ability to compete with their neighbours. 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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Wiley Free Content; Free Full-Text Journals in Chemistry |
| subjects | Anthraquinones - metabolism Anti-Bacterial Agents - metabolism Antibiotics Bacteria Bacterial Proteins - genetics Bacterial Proteins - metabolism Bacteriology Biological and medical sciences Biological Transport Biosensing Techniques Chemical synthesis DNA, Bacterial - metabolism Fundamental and applied biological sciences. Psychology Gene expression Gene Expression Regulation, Bacterial - drug effects Ligands Microbiology Miscellaneous Molecular biology Multigene Family Mutation Naphthalenes - metabolism Naphthoquinones - metabolism Pyrans - metabolism Repressor Proteins - drug effects Repressor Proteins - genetics Repressor Proteins - metabolism Streptomyces coelicolor Streptomyces coelicolor - drug effects Streptomyces coelicolor - genetics Streptomyces coelicolor - metabolism Tetracycline - pharmacology |
| title | Initiation of actinorhodin export in Streptomyces coelicolor |
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