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Synthetic biology approaches and combinatorial biosynthesis towards heterologous lipopeptide production† †Electronic supplementary information (ESI) available: Experimental procedures, design of artificial gene cluster, genetic manipulation, LC-MS analysis and structure elucidation. See DOI: 10.1039/c8sc02046a
Synthetic biology techniques coupled with heterologous secondary metabolite production offer opportunities for the discovery and optimisation of natural products. Synthetic biology techniques coupled with heterologous secondary metabolite production offer opportunities for the discovery and optimisa...
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Published in: | Chemical science (Cambridge) 2018-08, Vol.9 (38), p.7510-7519 |
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creator | Yan, Fu Burgard, Christian Popoff, Alexander Zaburannyi, Nestor Zipf, Gregor Maier, Josef Bernauer, Hubert S. Wenzel, Silke C. Müller, Rolf |
description | Synthetic biology techniques coupled with heterologous secondary metabolite production offer opportunities for the discovery and optimisation of natural products.
Synthetic biology techniques coupled with heterologous secondary metabolite production offer opportunities for the discovery and optimisation of natural products. Here we developed a new assembly strategy based on type IIS endonucleases and elaborate synthetic DNA platforms, which could be used to seamlessly assemble and engineer biosynthetic gene clusters (BGCs). By applying this versatile tool, we designed and assembled more than thirty different artificial myxochromide BGCs, each around 30 kb in size, and established heterologous expression platforms using a derivative of
Myxococcus xanthus
DK1622 as a host. In addition to the five native types of myxochromides (A, B, C, D and S), novel lipopeptide structures were produced by combinatorial exchange of nonribosomal peptide synthetase (NRPS) encoding genes from different myxochromide BGCs. Inspired by the evolutionary diversification of the native myxochromide megasynthetases, the ancestral A-type NRPS was engineered by inactivation, deletion, or duplication of catalytic domains and successfully converted into functional B-, C- and D-type megasynthetases. The constructional design approach applied in this study enables combinatorial engineering of complex synthetic BGCs and has great potential for the exploitation of other natural product biosynthetic pathways. |
doi_str_mv | 10.1039/c8sc02046a |
format | article |
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Synthetic biology techniques coupled with heterologous secondary metabolite production offer opportunities for the discovery and optimisation of natural products. Here we developed a new assembly strategy based on type IIS endonucleases and elaborate synthetic DNA platforms, which could be used to seamlessly assemble and engineer biosynthetic gene clusters (BGCs). By applying this versatile tool, we designed and assembled more than thirty different artificial myxochromide BGCs, each around 30 kb in size, and established heterologous expression platforms using a derivative of
Myxococcus xanthus
DK1622 as a host. In addition to the five native types of myxochromides (A, B, C, D and S), novel lipopeptide structures were produced by combinatorial exchange of nonribosomal peptide synthetase (NRPS) encoding genes from different myxochromide BGCs. Inspired by the evolutionary diversification of the native myxochromide megasynthetases, the ancestral A-type NRPS was engineered by inactivation, deletion, or duplication of catalytic domains and successfully converted into functional B-, C- and D-type megasynthetases. The constructional design approach applied in this study enables combinatorial engineering of complex synthetic BGCs and has great potential for the exploitation of other natural product biosynthetic pathways.</description><identifier>ISSN: 2041-6520</identifier><identifier>EISSN: 2041-6539</identifier><identifier>DOI: 10.1039/c8sc02046a</identifier><identifier>PMID: 30319751</identifier><language>eng</language><publisher>Royal Society of Chemistry</publisher><subject>Chemistry</subject><ispartof>Chemical science (Cambridge), 2018-08, Vol.9 (38), p.7510-7519</ispartof><rights>This journal is © The Royal Society of Chemistry 2018 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6180311/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6180311/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,733,786,790,891,27957,27958,53827,53829</link.rule.ids></links><search><creatorcontrib>Yan, Fu</creatorcontrib><creatorcontrib>Burgard, Christian</creatorcontrib><creatorcontrib>Popoff, Alexander</creatorcontrib><creatorcontrib>Zaburannyi, Nestor</creatorcontrib><creatorcontrib>Zipf, Gregor</creatorcontrib><creatorcontrib>Maier, Josef</creatorcontrib><creatorcontrib>Bernauer, Hubert S.</creatorcontrib><creatorcontrib>Wenzel, Silke C.</creatorcontrib><creatorcontrib>Müller, Rolf</creatorcontrib><title>Synthetic biology approaches and combinatorial biosynthesis towards heterologous lipopeptide production† †Electronic supplementary information (ESI) available: Experimental procedures, design of artificial gene cluster, genetic manipulation, LC-MS analysis and structure elucidation. See DOI: 10.1039/c8sc02046a</title><title>Chemical science (Cambridge)</title><description>Synthetic biology techniques coupled with heterologous secondary metabolite production offer opportunities for the discovery and optimisation of natural products.
Synthetic biology techniques coupled with heterologous secondary metabolite production offer opportunities for the discovery and optimisation of natural products. Here we developed a new assembly strategy based on type IIS endonucleases and elaborate synthetic DNA platforms, which could be used to seamlessly assemble and engineer biosynthetic gene clusters (BGCs). By applying this versatile tool, we designed and assembled more than thirty different artificial myxochromide BGCs, each around 30 kb in size, and established heterologous expression platforms using a derivative of
Myxococcus xanthus
DK1622 as a host. In addition to the five native types of myxochromides (A, B, C, D and S), novel lipopeptide structures were produced by combinatorial exchange of nonribosomal peptide synthetase (NRPS) encoding genes from different myxochromide BGCs. Inspired by the evolutionary diversification of the native myxochromide megasynthetases, the ancestral A-type NRPS was engineered by inactivation, deletion, or duplication of catalytic domains and successfully converted into functional B-, C- and D-type megasynthetases. The constructional design approach applied in this study enables combinatorial engineering of complex synthetic BGCs and has great potential for the exploitation of other natural product biosynthetic pathways.</description><subject>Chemistry</subject><issn>2041-6520</issn><issn>2041-6539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNqlUU1LAzEQXUXRor34C-ao0Nbdrv0UvNSKBcVDvS_T7LQdySYhyVb35k_xt_lLzC4iiEcDYSbkvTfvJVF0lsS9JE4nl2LsRNyPr4a4H7VCTbrDQTo5-On78XHUdu4lDitNk0F_dBQdp3GaTEaDpLV3vayU35JnASvWUm8qQGOsRrElB6hyELpYsUKvLaOsQa5hOHbg9Sva3EHgk63JunQg2WhDxnNOEITyUnjW6vP9A8KeSxLeahXGudIYSQUpj7YCVmttC6yhcD5fLi4Ad8gSV5KmMH8zZLmBylpTUF5ach3Ig42NAr0GtJ7XLGqLG1IEQpYumOo0pzpdgYpNKZsJHXiYdR-XIR7Kqg5S53TeBqtBF0iWgvMG2YMlEdw-Labw98FPo8M1Skft73oS3dzNn2f3XVOuCspF8GtRZiZYDxEzjZz9vlG8zTZ6lw2TcfiQJP23wBdDL7XG</recordid><startdate>20180808</startdate><enddate>20180808</enddate><creator>Yan, Fu</creator><creator>Burgard, Christian</creator><creator>Popoff, Alexander</creator><creator>Zaburannyi, Nestor</creator><creator>Zipf, Gregor</creator><creator>Maier, Josef</creator><creator>Bernauer, Hubert S.</creator><creator>Wenzel, Silke C.</creator><creator>Müller, Rolf</creator><general>Royal Society of Chemistry</general><scope>5PM</scope></search><sort><creationdate>20180808</creationdate><title>Synthetic biology approaches and combinatorial biosynthesis towards heterologous lipopeptide production† †Electronic supplementary information (ESI) available: Experimental procedures, design of artificial gene cluster, genetic manipulation, LC-MS analysis and structure elucidation. See DOI: 10.1039/c8sc02046a</title><author>Yan, Fu ; Burgard, Christian ; Popoff, Alexander ; Zaburannyi, Nestor ; Zipf, Gregor ; Maier, Josef ; Bernauer, Hubert S. ; Wenzel, Silke C. ; Müller, Rolf</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-pubmedcentral_primary_oai_pubmedcentral_nih_gov_61803113</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yan, Fu</creatorcontrib><creatorcontrib>Burgard, Christian</creatorcontrib><creatorcontrib>Popoff, Alexander</creatorcontrib><creatorcontrib>Zaburannyi, Nestor</creatorcontrib><creatorcontrib>Zipf, Gregor</creatorcontrib><creatorcontrib>Maier, Josef</creatorcontrib><creatorcontrib>Bernauer, Hubert S.</creatorcontrib><creatorcontrib>Wenzel, Silke C.</creatorcontrib><creatorcontrib>Müller, Rolf</creatorcontrib><collection>PubMed Central (Full Participant titles)</collection><jtitle>Chemical science (Cambridge)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yan, Fu</au><au>Burgard, Christian</au><au>Popoff, Alexander</au><au>Zaburannyi, Nestor</au><au>Zipf, Gregor</au><au>Maier, Josef</au><au>Bernauer, Hubert S.</au><au>Wenzel, Silke C.</au><au>Müller, Rolf</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthetic biology approaches and combinatorial biosynthesis towards heterologous lipopeptide production† †Electronic supplementary information (ESI) available: Experimental procedures, design of artificial gene cluster, genetic manipulation, LC-MS analysis and structure elucidation. See DOI: 10.1039/c8sc02046a</atitle><jtitle>Chemical science (Cambridge)</jtitle><date>2018-08-08</date><risdate>2018</risdate><volume>9</volume><issue>38</issue><spage>7510</spage><epage>7519</epage><pages>7510-7519</pages><issn>2041-6520</issn><eissn>2041-6539</eissn><notes>These authors contributed equally.</notes><abstract>Synthetic biology techniques coupled with heterologous secondary metabolite production offer opportunities for the discovery and optimisation of natural products.
Synthetic biology techniques coupled with heterologous secondary metabolite production offer opportunities for the discovery and optimisation of natural products. Here we developed a new assembly strategy based on type IIS endonucleases and elaborate synthetic DNA platforms, which could be used to seamlessly assemble and engineer biosynthetic gene clusters (BGCs). By applying this versatile tool, we designed and assembled more than thirty different artificial myxochromide BGCs, each around 30 kb in size, and established heterologous expression platforms using a derivative of
Myxococcus xanthus
DK1622 as a host. In addition to the five native types of myxochromides (A, B, C, D and S), novel lipopeptide structures were produced by combinatorial exchange of nonribosomal peptide synthetase (NRPS) encoding genes from different myxochromide BGCs. Inspired by the evolutionary diversification of the native myxochromide megasynthetases, the ancestral A-type NRPS was engineered by inactivation, deletion, or duplication of catalytic domains and successfully converted into functional B-, C- and D-type megasynthetases. The constructional design approach applied in this study enables combinatorial engineering of complex synthetic BGCs and has great potential for the exploitation of other natural product biosynthetic pathways.</abstract><pub>Royal Society of Chemistry</pub><pmid>30319751</pmid><doi>10.1039/c8sc02046a</doi><oa>free_for_read</oa></addata></record> |
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title | Synthetic biology approaches and combinatorial biosynthesis towards heterologous lipopeptide production† †Electronic supplementary information (ESI) available: Experimental procedures, design of artificial gene cluster, genetic manipulation, LC-MS analysis and structure elucidation. See DOI: 10.1039/c8sc02046a |
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