Biosynthesis of fredericamycin A, a new antitumor antibiotic
Fredericamycin A (FM A), produced by a strain of Streptomyces griseus, represents a new structural class of antitumor antibiotics containing a spiro ring system. Studies on the producer organism showed that glucose in the fermentation medium is not utilized until late in the growth stage, just prior...
Gespeichert in:
| Veröffentlicht in: | Biochemistry (Easton) 1985-01, Vol.24 (2), p.478-486 |
|---|---|
| Hauptverfasser: | , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 486 |
|---|---|
| container_issue | 2 |
| container_start_page | 478 |
| container_title | Biochemistry (Easton) |
| container_volume | 24 |
| creator | Byrne, Kevin M Hilton, Bruce D White, Richard J Misra, Renuka Pandey, Ramesh C |
| description | Fredericamycin A (FM A), produced by a strain of Streptomyces griseus, represents a new structural class of antitumor antibiotics containing a spiro ring system. Studies on the producer organism showed that glucose in the fermentation medium is not utilized until late in the growth stage, just prior to synthesis of FM A. [14C]Glucose tracer experiments demonstrated that glucose is incorporated into FM A by catabolism to acetate. Biosynthetic enrichment of FM A with single- and double-labeled [13C]acetate showed that the entire carbon skeleton of the spiro ring system is derived from acetate. L-Methionine was shown to provide the only nonskeletal carbon in FM A, the methoxy carbon at position C-6. The direction of the polyketide chain and the position of the carbon lost during biosynthesis were established by using stable isotope experiments. A general model for FM A biosynthesis is proposed, and a possible scheme for the formation of the spiro carbon center is presented. |
| doi_str_mv | 10.1021/bi00323a035 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_76034221</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>14100792</sourcerecordid><originalsourceid>FETCH-LOGICAL-a414t-4a86fe3578c69b1be03c4b76d35663bfccc05d7520529297341143452d6b918e3</originalsourceid><addsrcrecordid>eNqFkc1Lw0AQxRdRav04eRZyED1odPY7C16sqBUEBSsel81mg1ubRHcTtP-90ZbiQfA0M7wfM483CO1hOMVA8FnuASihBihfQ0PMCaRMKb6OhgAgUqIEbKKtGKf9yECyARpQhZUUZIjOR76J87p9cdHHpCmTMrjCBW9NNbe-Ti5OEpPU7iMxdevbrmrCT5f7pvV2B22UZhbd7rJuo6frq8nlOL27v7m9vLhLDcOsTZnJROkol5kVKse5A2pZLkVBuRA0L621wAvZ--ZEESUpw5hRxkkhcoUzR7fR4WLvW2jeOxdbXflo3Wxmatd0UUsBlBGC_wUxwwBSkR48XoA2NDEGV-q34CsT5hqD_g5V_wq1p_eXa7u8csWKXabY6wdL3URrZmUwtfVxhWWMZP0jeixdYD627nMlm_CqhaSS68nDo1aj5wxn45H-Pnu04I2Netp0oe5D_tPgF6Jql0c</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>14100792</pqid></control><display><type>article</type><title>Biosynthesis of fredericamycin A, a new antitumor antibiotic</title><source>MEDLINE</source><source>ACS Publications</source><creator>Byrne, Kevin M ; Hilton, Bruce D ; White, Richard J ; Misra, Renuka ; Pandey, Ramesh C</creator><creatorcontrib>Byrne, Kevin M ; Hilton, Bruce D ; White, Richard J ; Misra, Renuka ; Pandey, Ramesh C</creatorcontrib><description>Fredericamycin A (FM A), produced by a strain of Streptomyces griseus, represents a new structural class of antitumor antibiotics containing a spiro ring system. Studies on the producer organism showed that glucose in the fermentation medium is not utilized until late in the growth stage, just prior to synthesis of FM A. [14C]Glucose tracer experiments demonstrated that glucose is incorporated into FM A by catabolism to acetate. Biosynthetic enrichment of FM A with single- and double-labeled [13C]acetate showed that the entire carbon skeleton of the spiro ring system is derived from acetate. L-Methionine was shown to provide the only nonskeletal carbon in FM A, the methoxy carbon at position C-6. The direction of the polyketide chain and the position of the carbon lost during biosynthesis were established by using stable isotope experiments. A general model for FM A biosynthesis is proposed, and a possible scheme for the formation of the spiro carbon center is presented.</description><identifier>ISSN: 0006-2960</identifier><identifier>EISSN: 1520-4995</identifier><identifier>DOI: 10.1021/bi00323a035</identifier><identifier>PMID: 3919762</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>Acetates - metabolism ; Acetic Acid ; Antibiotics, Antineoplastic - biosynthesis ; Bioconversions. Hemisynthesis ; Biological and medical sciences ; Biotechnology ; fredericamycin A ; Fundamental and applied biological sciences. Psychology ; Glucose - metabolism ; Malonates - metabolism ; Methods. Procedures. Technologies ; Streptomyces griseus ; Streptomyces griseus - metabolism</subject><ispartof>Biochemistry (Easton), 1985-01, Vol.24 (2), p.478-486</ispartof><rights>1986 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a414t-4a86fe3578c69b1be03c4b76d35663bfccc05d7520529297341143452d6b918e3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/bi00323a035$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/bi00323a035$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,780,784,2765,27076,27924,27925,56738,56788</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=8428006$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/3919762$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Byrne, Kevin M</creatorcontrib><creatorcontrib>Hilton, Bruce D</creatorcontrib><creatorcontrib>White, Richard J</creatorcontrib><creatorcontrib>Misra, Renuka</creatorcontrib><creatorcontrib>Pandey, Ramesh C</creatorcontrib><title>Biosynthesis of fredericamycin A, a new antitumor antibiotic</title><title>Biochemistry (Easton)</title><addtitle>Biochemistry</addtitle><description>Fredericamycin A (FM A), produced by a strain of Streptomyces griseus, represents a new structural class of antitumor antibiotics containing a spiro ring system. Studies on the producer organism showed that glucose in the fermentation medium is not utilized until late in the growth stage, just prior to synthesis of FM A. [14C]Glucose tracer experiments demonstrated that glucose is incorporated into FM A by catabolism to acetate. Biosynthetic enrichment of FM A with single- and double-labeled [13C]acetate showed that the entire carbon skeleton of the spiro ring system is derived from acetate. L-Methionine was shown to provide the only nonskeletal carbon in FM A, the methoxy carbon at position C-6. The direction of the polyketide chain and the position of the carbon lost during biosynthesis were established by using stable isotope experiments. A general model for FM A biosynthesis is proposed, and a possible scheme for the formation of the spiro carbon center is presented.</description><subject>Acetates - metabolism</subject><subject>Acetic Acid</subject><subject>Antibiotics, Antineoplastic - biosynthesis</subject><subject>Bioconversions. Hemisynthesis</subject><subject>Biological and medical sciences</subject><subject>Biotechnology</subject><subject>fredericamycin A</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Glucose - metabolism</subject><subject>Malonates - metabolism</subject><subject>Methods. Procedures. Technologies</subject><subject>Streptomyces griseus</subject><subject>Streptomyces griseus - metabolism</subject><issn>0006-2960</issn><issn>1520-4995</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1985</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1Lw0AQxRdRav04eRZyED1odPY7C16sqBUEBSsel81mg1ubRHcTtP-90ZbiQfA0M7wfM483CO1hOMVA8FnuASihBihfQ0PMCaRMKb6OhgAgUqIEbKKtGKf9yECyARpQhZUUZIjOR76J87p9cdHHpCmTMrjCBW9NNbe-Ti5OEpPU7iMxdevbrmrCT5f7pvV2B22UZhbd7rJuo6frq8nlOL27v7m9vLhLDcOsTZnJROkol5kVKse5A2pZLkVBuRA0L621wAvZ--ZEESUpw5hRxkkhcoUzR7fR4WLvW2jeOxdbXflo3Wxmatd0UUsBlBGC_wUxwwBSkR48XoA2NDEGV-q34CsT5hqD_g5V_wq1p_eXa7u8csWKXabY6wdL3URrZmUwtfVxhWWMZP0jeixdYD627nMlm_CqhaSS68nDo1aj5wxn45H-Pnu04I2Netp0oe5D_tPgF6Jql0c</recordid><startdate>19850101</startdate><enddate>19850101</enddate><creator>Byrne, Kevin M</creator><creator>Hilton, Bruce D</creator><creator>White, Richard J</creator><creator>Misra, Renuka</creator><creator>Pandey, Ramesh C</creator><general>American Chemical Society</general><scope>BSCLL</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>7QO</scope><scope>7T7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>19850101</creationdate><title>Biosynthesis of fredericamycin A, a new antitumor antibiotic</title><author>Byrne, Kevin M ; Hilton, Bruce D ; White, Richard J ; Misra, Renuka ; Pandey, Ramesh C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a414t-4a86fe3578c69b1be03c4b76d35663bfccc05d7520529297341143452d6b918e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1985</creationdate><topic>Acetates - metabolism</topic><topic>Acetic Acid</topic><topic>Antibiotics, Antineoplastic - biosynthesis</topic><topic>Bioconversions. Hemisynthesis</topic><topic>Biological and medical sciences</topic><topic>Biotechnology</topic><topic>fredericamycin A</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Glucose - metabolism</topic><topic>Malonates - metabolism</topic><topic>Methods. Procedures. Technologies</topic><topic>Streptomyces griseus</topic><topic>Streptomyces griseus - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Byrne, Kevin M</creatorcontrib><creatorcontrib>Hilton, Bruce D</creatorcontrib><creatorcontrib>White, Richard J</creatorcontrib><creatorcontrib>Misra, Renuka</creatorcontrib><creatorcontrib>Pandey, Ramesh C</creatorcontrib><collection>Istex</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>Biotechnology Research Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemistry (Easton)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Byrne, Kevin M</au><au>Hilton, Bruce D</au><au>White, Richard J</au><au>Misra, Renuka</au><au>Pandey, Ramesh C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Biosynthesis of fredericamycin A, a new antitumor antibiotic</atitle><jtitle>Biochemistry (Easton)</jtitle><addtitle>Biochemistry</addtitle><date>1985-01-01</date><risdate>1985</risdate><volume>24</volume><issue>2</issue><spage>478</spage><epage>486</epage><pages>478-486</pages><issn>0006-2960</issn><eissn>1520-4995</eissn><abstract>Fredericamycin A (FM A), produced by a strain of Streptomyces griseus, represents a new structural class of antitumor antibiotics containing a spiro ring system. Studies on the producer organism showed that glucose in the fermentation medium is not utilized until late in the growth stage, just prior to synthesis of FM A. [14C]Glucose tracer experiments demonstrated that glucose is incorporated into FM A by catabolism to acetate. Biosynthetic enrichment of FM A with single- and double-labeled [13C]acetate showed that the entire carbon skeleton of the spiro ring system is derived from acetate. L-Methionine was shown to provide the only nonskeletal carbon in FM A, the methoxy carbon at position C-6. The direction of the polyketide chain and the position of the carbon lost during biosynthesis were established by using stable isotope experiments. A general model for FM A biosynthesis is proposed, and a possible scheme for the formation of the spiro carbon center is presented.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><pmid>3919762</pmid><doi>10.1021/bi00323a035</doi><tpages>9</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0006-2960 |
| ispartof | Biochemistry (Easton), 1985-01, Vol.24 (2), p.478-486 |
| issn | 0006-2960 1520-4995 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_76034221 |
| source | MEDLINE; ACS Publications |
| subjects | Acetates - metabolism Acetic Acid Antibiotics, Antineoplastic - biosynthesis Bioconversions. Hemisynthesis Biological and medical sciences Biotechnology fredericamycin A Fundamental and applied biological sciences. Psychology Glucose - metabolism Malonates - metabolism Methods. Procedures. Technologies Streptomyces griseus Streptomyces griseus - metabolism |
| title | Biosynthesis of fredericamycin A, a new antitumor antibiotic |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-21T12%3A54%3A30IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Biosynthesis%20of%20fredericamycin%20A,%20a%20new%20antitumor%20antibiotic&rft.jtitle=Biochemistry%20(Easton)&rft.au=Byrne,%20Kevin%20M&rft.date=1985-01-01&rft.volume=24&rft.issue=2&rft.spage=478&rft.epage=486&rft.pages=478-486&rft.issn=0006-2960&rft.eissn=1520-4995&rft_id=info:doi/10.1021/bi00323a035&rft_dat=%3Cproquest_cross%3E14100792%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=14100792&rft_id=info:pmid/3919762&rfr_iscdi=true |