Novel Avilamycin Derivatives with Improved Polarity Generated by Targeted Gene Disruption
The oligosaccharide antibiotics avilamycin A and C are produced by Streptomyces viridochromogenes Tü57. Both consist of a heptasaccharide chain, which is attached to a polyketide-derived dichloroisoeverninic acid moiety. They show excellent antibiotic activity against Gram-positive bacteria. Both mo...
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| Veröffentlicht in: | Chemistry & biology 2004-10, Vol.11 (10), p.1403-1411 |
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| creator | Weitnauer, Gabriele Hauser, Gerd Hofmann, Carsten Linder, Ulrike Boll, Raija Pelz, Klaus Glaser, Steffen J. Bechthold, Andreas |
| description | The oligosaccharide antibiotics avilamycin A and C are produced by
Streptomyces viridochromogenes Tü57. Both consist of a heptasaccharide chain, which is attached to a polyketide-derived dichloroisoeverninic acid moiety. They show excellent antibiotic activity against Gram-positive bacteria. Both molecules are modified by O-methylation at different positions, which contributes to poor water solubility and difficulties in galenical drug development. In order to generate novel avilamycin derivatives with improved polarity and improved pharmacokinetic properties, we generated a series of mutants with one, two, or three mutated methyltransferase genes. Based on the structure of the novel avilamycin derivatives, the exact function of three methyltransferases, AviG2, AviG5, and AviG6, involved in avilamycin biosynthesis could be assigned. |
| doi_str_mv | 10.1016/j.chembiol.2004.08.016 |
| format | Article |
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Streptomyces viridochromogenes Tü57. Both consist of a heptasaccharide chain, which is attached to a polyketide-derived dichloroisoeverninic acid moiety. They show excellent antibiotic activity against Gram-positive bacteria. Both molecules are modified by O-methylation at different positions, which contributes to poor water solubility and difficulties in galenical drug development. In order to generate novel avilamycin derivatives with improved polarity and improved pharmacokinetic properties, we generated a series of mutants with one, two, or three mutated methyltransferase genes. Based on the structure of the novel avilamycin derivatives, the exact function of three methyltransferases, AviG2, AviG5, and AviG6, involved in avilamycin biosynthesis could be assigned.</description><identifier>ISSN: 1074-5521</identifier><identifier>EISSN: 1879-1301</identifier><identifier>DOI: 10.1016/j.chembiol.2004.08.016</identifier><identifier>PMID: 15489167</identifier><language>eng</language><publisher>United States: Elsevier Ltd</publisher><subject>Gene Targeting - methods ; Gram-Positive Bacteria - drug effects ; Methyltransferases - genetics ; Methyltransferases - metabolism ; Microbial Sensitivity Tests ; Molecular Sequence Data ; Multigene Family ; Nuclear Magnetic Resonance, Biomolecular ; Oligosaccharides - chemistry ; Oligosaccharides - genetics ; Oligosaccharides - metabolism ; Oligosaccharides - pharmacology ; Streptomyces - enzymology ; Streptomyces - genetics</subject><ispartof>Chemistry & biology, 2004-10, Vol.11 (10), p.1403-1411</ispartof><rights>2004 Elsevier Ltd</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c412t-61bfd64a3e54a3cfc8ceffe33d727eef822fdd6af4515ef9edee0e73c3a9b06a3</citedby><cites>FETCH-LOGICAL-c412t-61bfd64a3e54a3cfc8ceffe33d727eef822fdd6af4515ef9edee0e73c3a9b06a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1074552104002522$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15489167$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Weitnauer, Gabriele</creatorcontrib><creatorcontrib>Hauser, Gerd</creatorcontrib><creatorcontrib>Hofmann, Carsten</creatorcontrib><creatorcontrib>Linder, Ulrike</creatorcontrib><creatorcontrib>Boll, Raija</creatorcontrib><creatorcontrib>Pelz, Klaus</creatorcontrib><creatorcontrib>Glaser, Steffen J.</creatorcontrib><creatorcontrib>Bechthold, Andreas</creatorcontrib><title>Novel Avilamycin Derivatives with Improved Polarity Generated by Targeted Gene Disruption</title><title>Chemistry & biology</title><addtitle>Chem Biol</addtitle><description>The oligosaccharide antibiotics avilamycin A and C are produced by
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Based on the structure of the novel avilamycin derivatives, the exact function of three methyltransferases, AviG2, AviG5, and AviG6, involved in avilamycin biosynthesis could be assigned.</description><subject>Gene Targeting - methods</subject><subject>Gram-Positive Bacteria - drug effects</subject><subject>Methyltransferases - genetics</subject><subject>Methyltransferases - metabolism</subject><subject>Microbial Sensitivity Tests</subject><subject>Molecular Sequence Data</subject><subject>Multigene Family</subject><subject>Nuclear Magnetic Resonance, Biomolecular</subject><subject>Oligosaccharides - chemistry</subject><subject>Oligosaccharides - genetics</subject><subject>Oligosaccharides - metabolism</subject><subject>Oligosaccharides - pharmacology</subject><subject>Streptomyces - enzymology</subject><subject>Streptomyces - genetics</subject><issn>1074-5521</issn><issn>1879-1301</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkMtOwzAQRS0EolD4hSordgl2Ho6zo2qhVKqARVmwshx7TF3lUewkqH-PqxaxZDMzujrzughNCI4IJvR-G8kN1KVpqyjGOI0wi7x8hq4Iy4uQJJic-xrnaZhlMRmha-e2GGPCCnqJRiRLWUFofoU-XtoBqmA6mErUe2maYA7WDKIzA7jg23SbYFnvrIdU8NZWwppuHyygASs6L5X7YC3sJxzqgxrMjbP9rjNtc4MutKgc3J7yGL0_Pa5nz-HqdbGcTVehTEnchZSUWtFUJJD5ILVkErSGJFF5nANoFsdaKSp0mpEMdAEKAEOeyEQUJaYiGaO741x_5VcPruO1cRKqSjTQ9o5TWuQJY7kH6RGUtnXOguY7a2ph95xgfjCVb_mvqfxgKseMe9k3Tk4b-rIG9dd2ctEDD0cA_J-DAcudNNBIUMaC7LhqzX87fgCXk46p</recordid><startdate>20041001</startdate><enddate>20041001</enddate><creator>Weitnauer, Gabriele</creator><creator>Hauser, Gerd</creator><creator>Hofmann, Carsten</creator><creator>Linder, Ulrike</creator><creator>Boll, Raija</creator><creator>Pelz, Klaus</creator><creator>Glaser, Steffen J.</creator><creator>Bechthold, Andreas</creator><general>Elsevier Ltd</general><scope>6I.</scope><scope>AAFTH</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>7X8</scope></search><sort><creationdate>20041001</creationdate><title>Novel Avilamycin Derivatives with Improved Polarity Generated by Targeted Gene Disruption</title><author>Weitnauer, Gabriele ; Hauser, Gerd ; Hofmann, Carsten ; Linder, Ulrike ; Boll, Raija ; Pelz, Klaus ; Glaser, Steffen J. ; Bechthold, Andreas</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c412t-61bfd64a3e54a3cfc8ceffe33d727eef822fdd6af4515ef9edee0e73c3a9b06a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Gene Targeting - methods</topic><topic>Gram-Positive Bacteria - drug effects</topic><topic>Methyltransferases - genetics</topic><topic>Methyltransferases - metabolism</topic><topic>Microbial Sensitivity Tests</topic><topic>Molecular Sequence Data</topic><topic>Multigene Family</topic><topic>Nuclear Magnetic Resonance, Biomolecular</topic><topic>Oligosaccharides - chemistry</topic><topic>Oligosaccharides - genetics</topic><topic>Oligosaccharides - metabolism</topic><topic>Oligosaccharides - pharmacology</topic><topic>Streptomyces - enzymology</topic><topic>Streptomyces - genetics</topic><toplevel>online_resources</toplevel><creatorcontrib>Weitnauer, Gabriele</creatorcontrib><creatorcontrib>Hauser, Gerd</creatorcontrib><creatorcontrib>Hofmann, Carsten</creatorcontrib><creatorcontrib>Linder, Ulrike</creatorcontrib><creatorcontrib>Boll, Raija</creatorcontrib><creatorcontrib>Pelz, Klaus</creatorcontrib><creatorcontrib>Glaser, Steffen J.</creatorcontrib><creatorcontrib>Bechthold, Andreas</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Chemistry & biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Weitnauer, Gabriele</au><au>Hauser, Gerd</au><au>Hofmann, Carsten</au><au>Linder, Ulrike</au><au>Boll, Raija</au><au>Pelz, Klaus</au><au>Glaser, Steffen J.</au><au>Bechthold, Andreas</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Novel Avilamycin Derivatives with Improved Polarity Generated by Targeted Gene Disruption</atitle><jtitle>Chemistry & biology</jtitle><addtitle>Chem Biol</addtitle><date>2004-10-01</date><risdate>2004</risdate><volume>11</volume><issue>10</issue><spage>1403</spage><epage>1411</epage><pages>1403-1411</pages><issn>1074-5521</issn><eissn>1879-1301</eissn><abstract>The oligosaccharide antibiotics avilamycin A and C are produced by
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| source | MEDLINE; Cell Press Free Archives; Elsevier ScienceDirect Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Free Full-Text Journals in Chemistry |
| subjects | Gene Targeting - methods Gram-Positive Bacteria - drug effects Methyltransferases - genetics Methyltransferases - metabolism Microbial Sensitivity Tests Molecular Sequence Data Multigene Family Nuclear Magnetic Resonance, Biomolecular Oligosaccharides - chemistry Oligosaccharides - genetics Oligosaccharides - metabolism Oligosaccharides - pharmacology Streptomyces - enzymology Streptomyces - genetics |
| title | Novel Avilamycin Derivatives with Improved Polarity Generated by Targeted Gene Disruption |
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