Biosynthetic Origin of the Methoxyl Extender Unit in Bafilomycin and Concanamycin using Stereospecifically Labeled Precursors
The microbial macrolides bafilomycin A 1 , B 1 and concanamycin A from Streptomyces spp. are potent and specific inhibitors of V-ATPases. The question of the biosynthetic origin of the two uncommon “glycolate units” of each of the macrolide structures was addressed by feeding experiments with stereo...
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| Veröffentlicht in: | Journal of antibiotics 2007-01, Vol.60 (1), p.52-60 |
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| creator | Schuhmann, Tim Vollmar, Daniel Grond, Stephanie |
| description | The microbial macrolides bafilomycin A
1
, B
1
and concanamycin A from
Streptomyces
spp. are potent and specific inhibitors of V-ATPases. The question of the biosynthetic origin of the two uncommon “glycolate units” of each of the macrolide structures was addressed by feeding experiments with stereospecifically
13
C-labeled precursors. Our studies clearly indicate that glycerol is a source for the methoxylated C
2
-units and determines the orientation of the incorporation. Products from the carboxylic acid pool or TCA cycle are ruled out as key precursors. The data suggest the action of a glycerol kinase and point to phosphoglycerate as an intermediate in their biosynthesis. However, glycerate itself is not accepted as a precursor. We present the likely biosynthetic pathway and show the value of stereospecifically labeled presursors as an important tool for biosynthetic investigations. |
| doi_str_mv | 10.1038/ja.2007.7 |
| format | Article |
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1
, B
1
and concanamycin A from
Streptomyces
spp. are potent and specific inhibitors of V-ATPases. The question of the biosynthetic origin of the two uncommon “glycolate units” of each of the macrolide structures was addressed by feeding experiments with stereospecifically
13
C-labeled precursors. Our studies clearly indicate that glycerol is a source for the methoxylated C
2
-units and determines the orientation of the incorporation. Products from the carboxylic acid pool or TCA cycle are ruled out as key precursors. The data suggest the action of a glycerol kinase and point to phosphoglycerate as an intermediate in their biosynthesis. However, glycerate itself is not accepted as a precursor. We present the likely biosynthetic pathway and show the value of stereospecifically labeled presursors as an important tool for biosynthetic investigations.</description><identifier>ISSN: 0021-8820</identifier><identifier>EISSN: 1881-1469</identifier><identifier>DOI: 10.1038/ja.2007.7</identifier><identifier>PMID: 17390589</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Bacteriology ; Biomedical and Life Sciences ; Bioorganic Chemistry ; Biosynthesis ; Carbon Isotopes - metabolism ; Carboxylic Acids ; Citric Acid Cycle ; Glycerol - metabolism ; Glycerol Kinase - metabolism ; Glycolates - metabolism ; Life Sciences ; Macrolides - metabolism ; Medicinal Chemistry ; Metabolic Networks and Pathways ; Microbiology ; Molecular Structure ; Organic Chemistry ; original-article ; Streptomyces - metabolism</subject><ispartof>Journal of antibiotics, 2007-01, Vol.60 (1), p.52-60</ispartof><rights>Japan Antibiotics Research Association 2007</rights><rights>Copyright Nature Publishing Group Jan 2007</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c410t-c7574154e1ea65eb4cccd5dbff08d28de9c6c9f1261eebaa55e5675208e39023</citedby><cites>FETCH-LOGICAL-c410t-c7574154e1ea65eb4cccd5dbff08d28de9c6c9f1261eebaa55e5675208e39023</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17390589$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Schuhmann, Tim</creatorcontrib><creatorcontrib>Vollmar, Daniel</creatorcontrib><creatorcontrib>Grond, Stephanie</creatorcontrib><title>Biosynthetic Origin of the Methoxyl Extender Unit in Bafilomycin and Concanamycin using Stereospecifically Labeled Precursors</title><title>Journal of antibiotics</title><addtitle>J Antibiot</addtitle><addtitle>J Antibiot (Tokyo)</addtitle><description>The microbial macrolides bafilomycin A
1
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1
and concanamycin A from
Streptomyces
spp. are potent and specific inhibitors of V-ATPases. The question of the biosynthetic origin of the two uncommon “glycolate units” of each of the macrolide structures was addressed by feeding experiments with stereospecifically
13
C-labeled precursors. Our studies clearly indicate that glycerol is a source for the methoxylated C
2
-units and determines the orientation of the incorporation. Products from the carboxylic acid pool or TCA cycle are ruled out as key precursors. The data suggest the action of a glycerol kinase and point to phosphoglycerate as an intermediate in their biosynthesis. However, glycerate itself is not accepted as a precursor. We present the likely biosynthetic pathway and show the value of stereospecifically labeled presursors as an important tool for biosynthetic investigations.</description><subject>Bacteriology</subject><subject>Biomedical and Life Sciences</subject><subject>Bioorganic Chemistry</subject><subject>Biosynthesis</subject><subject>Carbon Isotopes - metabolism</subject><subject>Carboxylic Acids</subject><subject>Citric Acid Cycle</subject><subject>Glycerol - metabolism</subject><subject>Glycerol Kinase - metabolism</subject><subject>Glycolates - metabolism</subject><subject>Life Sciences</subject><subject>Macrolides - metabolism</subject><subject>Medicinal Chemistry</subject><subject>Metabolic Networks and Pathways</subject><subject>Microbiology</subject><subject>Molecular Structure</subject><subject>Organic Chemistry</subject><subject>original-article</subject><subject>Streptomyces - metabolism</subject><issn>0021-8820</issn><issn>1881-1469</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNpl0V1r2zAUBmAxVta028X-wBAMCis4O7ItS75sQr8gpYV110KWj1MFR8okG-qL_vepJLDRXkkcPbySeAn5ymDOoJA_N3qeA4i5-EBmTEqWsbKqP5IZQM4yKXM4JicxbgAKUQj5iRwzUdTAZT0jLwvr4-SGJxysoffBrq2jvqNpQO9wePLPU08vnwd0LQb629mBJrDQne39djJpr11Ll94Z7fR-MEbr1vTXgAF93KGxnTW67ye60g322NKHgGYM0Yf4mRx1uo_45bCeksery8flTba6v75dXqwyUzIYMiO4KBkvkaGuODalMablbdN1INtctlibytQdyyuG2GjNOfJK8Bwkpn_mxSk528fugv8zYhzU1kaDfa8d-jEqAQUDyWWC39_AjR-DS09TTEghoQJRJ_Vjr0zwMQbs1C7YrQ6TYqBeC1EbrV4LUSLZb4fEsdli-08eGkjgfA9iOnJrDP9d-S7tL6wDljs</recordid><startdate>20070101</startdate><enddate>20070101</enddate><creator>Schuhmann, Tim</creator><creator>Vollmar, Daniel</creator><creator>Grond, Stephanie</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><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>3V.</scope><scope>7QL</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>20070101</creationdate><title>Biosynthetic Origin of the Methoxyl Extender Unit in Bafilomycin and Concanamycin using Stereospecifically Labeled Precursors</title><author>Schuhmann, Tim ; Vollmar, Daniel ; Grond, Stephanie</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c410t-c7574154e1ea65eb4cccd5dbff08d28de9c6c9f1261eebaa55e5675208e39023</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Bacteriology</topic><topic>Biomedical and Life Sciences</topic><topic>Bioorganic Chemistry</topic><topic>Biosynthesis</topic><topic>Carbon Isotopes - metabolism</topic><topic>Carboxylic Acids</topic><topic>Citric Acid Cycle</topic><topic>Glycerol - metabolism</topic><topic>Glycerol Kinase - metabolism</topic><topic>Glycolates - metabolism</topic><topic>Life Sciences</topic><topic>Macrolides - metabolism</topic><topic>Medicinal Chemistry</topic><topic>Metabolic Networks and Pathways</topic><topic>Microbiology</topic><topic>Molecular Structure</topic><topic>Organic Chemistry</topic><topic>original-article</topic><topic>Streptomyces - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schuhmann, Tim</creatorcontrib><creatorcontrib>Vollmar, Daniel</creatorcontrib><creatorcontrib>Grond, Stephanie</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of antibiotics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Schuhmann, Tim</au><au>Vollmar, Daniel</au><au>Grond, Stephanie</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Biosynthetic Origin of the Methoxyl Extender Unit in Bafilomycin and Concanamycin using Stereospecifically Labeled Precursors</atitle><jtitle>Journal of antibiotics</jtitle><stitle>J Antibiot</stitle><addtitle>J Antibiot (Tokyo)</addtitle><date>2007-01-01</date><risdate>2007</risdate><volume>60</volume><issue>1</issue><spage>52</spage><epage>60</epage><pages>52-60</pages><issn>0021-8820</issn><eissn>1881-1469</eissn><abstract>The microbial macrolides bafilomycin A
1
, B
1
and concanamycin A from
Streptomyces
spp. are potent and specific inhibitors of V-ATPases. The question of the biosynthetic origin of the two uncommon “glycolate units” of each of the macrolide structures was addressed by feeding experiments with stereospecifically
13
C-labeled precursors. Our studies clearly indicate that glycerol is a source for the methoxylated C
2
-units and determines the orientation of the incorporation. Products from the carboxylic acid pool or TCA cycle are ruled out as key precursors. The data suggest the action of a glycerol kinase and point to phosphoglycerate as an intermediate in their biosynthesis. However, glycerate itself is not accepted as a precursor. We present the likely biosynthetic pathway and show the value of stereospecifically labeled presursors as an important tool for biosynthetic investigations.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>17390589</pmid><doi>10.1038/ja.2007.7</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
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| ispartof | Journal of antibiotics, 2007-01, Vol.60 (1), p.52-60 |
| issn | 0021-8820 1881-1469 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_70310858 |
| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Bacteriology Biomedical and Life Sciences Bioorganic Chemistry Biosynthesis Carbon Isotopes - metabolism Carboxylic Acids Citric Acid Cycle Glycerol - metabolism Glycerol Kinase - metabolism Glycolates - metabolism Life Sciences Macrolides - metabolism Medicinal Chemistry Metabolic Networks and Pathways Microbiology Molecular Structure Organic Chemistry original-article Streptomyces - metabolism |
| title | Biosynthetic Origin of the Methoxyl Extender Unit in Bafilomycin and Concanamycin using Stereospecifically Labeled Precursors |
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