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Reconstitution of a 10-gene pathway for synthesis of the plant alkaloid dihydrosanguinarine in Saccharomyces cerevisiae
Benzylisoquinoline alkaloids (BIAs) represent a large class of plant secondary metabolites, including pharmaceuticals such as morphine, codeine and their derivatives. Large-scale production of BIA-based pharmaceuticals is limited to extraction and derivatization of alkaloids that accumulate in plant...
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| Published in: | Nature communications 2014-02, Vol.5 (1), p.3283-3283, Article 3283 |
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| creator | Fossati, Elena Ekins, Andrew Narcross, Lauren Zhu, Yun Falgueyret, Jean-Pierre Beaudoin, Guillaume A. W. Facchini, Peter J Martin, Vincent J. J. |
| description | Benzylisoquinoline alkaloids (BIAs) represent a large class of plant secondary metabolites, including pharmaceuticals such as morphine, codeine and their derivatives. Large-scale production of BIA-based pharmaceuticals is limited to extraction and derivatization of alkaloids that accumulate
in planta
. Synthesis of BIAs in microbial hosts could bypass such limitations and transform both industrial production of BIAs with recognized value and research into uncharacterized BIAs. Here we reconstitute a 10-gene plant pathway in
Saccharomyces cerevisiae
that allows for the production of dihydrosanguinarine and its oxidized derivative sanguinarine from (
R,S
)-norlaudanosoline. Synthesis of dihydrosanguinarine also yields the side-products
N
-methylscoulerine and
N
-methylcheilanthifoline, the latter of which has not been detected in plants. This work represents the longest reconstituted alkaloid pathway ever assembled in yeast and demonstrates the feasibility of the production of high-value alkaloids in microbial systems.
Benzylisoquinoline alkaloids are a group of plant secondary metabolites with important pharmaceutical applications. Here, the authors have reconstituted a 10-gene alkaloid pathway in
Saccharomyces cerevisiae
, demonstrating the feasibility of producing commercially important alkaloids in microbial systems. |
| doi_str_mv | 10.1038/ncomms4283 |
| format | article |
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in planta
. Synthesis of BIAs in microbial hosts could bypass such limitations and transform both industrial production of BIAs with recognized value and research into uncharacterized BIAs. Here we reconstitute a 10-gene plant pathway in
Saccharomyces cerevisiae
that allows for the production of dihydrosanguinarine and its oxidized derivative sanguinarine from (
R,S
)-norlaudanosoline. Synthesis of dihydrosanguinarine also yields the side-products
N
-methylscoulerine and
N
-methylcheilanthifoline, the latter of which has not been detected in plants. This work represents the longest reconstituted alkaloid pathway ever assembled in yeast and demonstrates the feasibility of the production of high-value alkaloids in microbial systems.
Benzylisoquinoline alkaloids are a group of plant secondary metabolites with important pharmaceutical applications. Here, the authors have reconstituted a 10-gene alkaloid pathway in
Saccharomyces cerevisiae
, demonstrating the feasibility of producing commercially important alkaloids in microbial systems.</description><identifier>ISSN: 2041-1723</identifier><identifier>EISSN: 2041-1723</identifier><identifier>DOI: 10.1038/ncomms4283</identifier><identifier>PMID: 24513861</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/61/338/318 ; Alkaloids - biosynthesis ; Benzophenanthridines - biosynthesis ; Genes, Plant ; Genetic Vectors ; Humanities and Social Sciences ; Isoquinolines ; multidisciplinary ; Papaver - genetics ; Papaver - metabolism ; Plasmids ; Saccharomyces cerevisiae - genetics ; Saccharomyces cerevisiae - metabolism ; Science ; Science (multidisciplinary) ; Tetrahydropapaveroline - metabolism ; Transformation, Genetic - genetics</subject><ispartof>Nature communications, 2014-02, Vol.5 (1), p.3283-3283, Article 3283</ispartof><rights>Springer Nature Limited 2014</rights><rights>Copyright Nature Publishing Group Feb 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c453t-f2eb0a9b22e4d960128627b55b117424983b1bf76c960bf72a26f2b7467cf4dc3</citedby><cites>FETCH-LOGICAL-c453t-f2eb0a9b22e4d960128627b55b117424983b1bf76c960bf72a26f2b7467cf4dc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1496949271/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1496949271?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,25753,27924,27925,37012,37013,44590,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24513861$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fossati, Elena</creatorcontrib><creatorcontrib>Ekins, Andrew</creatorcontrib><creatorcontrib>Narcross, Lauren</creatorcontrib><creatorcontrib>Zhu, Yun</creatorcontrib><creatorcontrib>Falgueyret, Jean-Pierre</creatorcontrib><creatorcontrib>Beaudoin, Guillaume A. W.</creatorcontrib><creatorcontrib>Facchini, Peter J</creatorcontrib><creatorcontrib>Martin, Vincent J. J.</creatorcontrib><title>Reconstitution of a 10-gene pathway for synthesis of the plant alkaloid dihydrosanguinarine in Saccharomyces cerevisiae</title><title>Nature communications</title><addtitle>Nat Commun</addtitle><addtitle>Nat Commun</addtitle><description>Benzylisoquinoline alkaloids (BIAs) represent a large class of plant secondary metabolites, including pharmaceuticals such as morphine, codeine and their derivatives. Large-scale production of BIA-based pharmaceuticals is limited to extraction and derivatization of alkaloids that accumulate
in planta
. Synthesis of BIAs in microbial hosts could bypass such limitations and transform both industrial production of BIAs with recognized value and research into uncharacterized BIAs. Here we reconstitute a 10-gene plant pathway in
Saccharomyces cerevisiae
that allows for the production of dihydrosanguinarine and its oxidized derivative sanguinarine from (
R,S
)-norlaudanosoline. Synthesis of dihydrosanguinarine also yields the side-products
N
-methylscoulerine and
N
-methylcheilanthifoline, the latter of which has not been detected in plants. This work represents the longest reconstituted alkaloid pathway ever assembled in yeast and demonstrates the feasibility of the production of high-value alkaloids in microbial systems.
Benzylisoquinoline alkaloids are a group of plant secondary metabolites with important pharmaceutical applications. Here, the authors have reconstituted a 10-gene alkaloid pathway in
Saccharomyces cerevisiae
, demonstrating the feasibility of producing commercially important alkaloids in microbial systems.</description><subject>631/61/338/318</subject><subject>Alkaloids - biosynthesis</subject><subject>Benzophenanthridines - biosynthesis</subject><subject>Genes, Plant</subject><subject>Genetic Vectors</subject><subject>Humanities and Social Sciences</subject><subject>Isoquinolines</subject><subject>multidisciplinary</subject><subject>Papaver - genetics</subject><subject>Papaver - metabolism</subject><subject>Plasmids</subject><subject>Saccharomyces cerevisiae - genetics</subject><subject>Saccharomyces cerevisiae - metabolism</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Tetrahydropapaveroline - metabolism</subject><subject>Transformation, Genetic - genetics</subject><issn>2041-1723</issn><issn>2041-1723</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><recordid>eNplkVlLw0AQxxdRbKl98QPIgi-iRLNHrkcpXlAQPJ7DZjNptia7dTex5Nu7pfVA52UG5jf_uRA6JuElCVl6paVpW8dpyvbQmIacBCShbP9XPEJT55ahN5aRlPNDNKI8IiyNyRitn0Aa7TrV9Z0yGpsKC0zCYAEa8Ep09VoMuDIWu0F3NTjlNoiP8KoRusOieRONUSUuVT2U1jihF73SwipfrzR-FlLWwpp2kOCwBAsfyikBR-igEo2D6c5P0OvtzcvsPpg_3j3MrueB5BHrgopCEYqsoBR4mcUhoWlMkyKKCkISTnmWsoIUVRJLn_SeChpXtEh4nMiKl5JN0NlWd2XNew-uy1vlJDR-eDC9ywnPMsLjlDGPnv5Bl6a32k-3oeKMZzQhnjrfUtIv6yxU-cqqVtghJ2G--Uj-8xEPn-wk-6KF8hv9ur8HLraA8ym9APur53-5T7S2lvU</recordid><startdate>20140211</startdate><enddate>20140211</enddate><creator>Fossati, Elena</creator><creator>Ekins, Andrew</creator><creator>Narcross, Lauren</creator><creator>Zhu, Yun</creator><creator>Falgueyret, Jean-Pierre</creator><creator>Beaudoin, Guillaume A. 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W.</au><au>Facchini, Peter J</au><au>Martin, Vincent J. J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Reconstitution of a 10-gene pathway for synthesis of the plant alkaloid dihydrosanguinarine in Saccharomyces cerevisiae</atitle><jtitle>Nature communications</jtitle><stitle>Nat Commun</stitle><addtitle>Nat Commun</addtitle><date>2014-02-11</date><risdate>2014</risdate><volume>5</volume><issue>1</issue><spage>3283</spage><epage>3283</epage><pages>3283-3283</pages><artnum>3283</artnum><issn>2041-1723</issn><eissn>2041-1723</eissn><abstract>Benzylisoquinoline alkaloids (BIAs) represent a large class of plant secondary metabolites, including pharmaceuticals such as morphine, codeine and their derivatives. Large-scale production of BIA-based pharmaceuticals is limited to extraction and derivatization of alkaloids that accumulate
in planta
. Synthesis of BIAs in microbial hosts could bypass such limitations and transform both industrial production of BIAs with recognized value and research into uncharacterized BIAs. Here we reconstitute a 10-gene plant pathway in
Saccharomyces cerevisiae
that allows for the production of dihydrosanguinarine and its oxidized derivative sanguinarine from (
R,S
)-norlaudanosoline. Synthesis of dihydrosanguinarine also yields the side-products
N
-methylscoulerine and
N
-methylcheilanthifoline, the latter of which has not been detected in plants. This work represents the longest reconstituted alkaloid pathway ever assembled in yeast and demonstrates the feasibility of the production of high-value alkaloids in microbial systems.
Benzylisoquinoline alkaloids are a group of plant secondary metabolites with important pharmaceutical applications. Here, the authors have reconstituted a 10-gene alkaloid pathway in
Saccharomyces cerevisiae
, demonstrating the feasibility of producing commercially important alkaloids in microbial systems.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>24513861</pmid><doi>10.1038/ncomms4283</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 631/61/338/318 Alkaloids - biosynthesis Benzophenanthridines - biosynthesis Genes, Plant Genetic Vectors Humanities and Social Sciences Isoquinolines multidisciplinary Papaver - genetics Papaver - metabolism Plasmids Saccharomyces cerevisiae - genetics Saccharomyces cerevisiae - metabolism Science Science (multidisciplinary) Tetrahydropapaveroline - metabolism Transformation, Genetic - genetics |
| title | Reconstitution of a 10-gene pathway for synthesis of the plant alkaloid dihydrosanguinarine in Saccharomyces cerevisiae |
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