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dc.contributor.authorYan, Fu
dc.contributor.authorBurgard, Christian
dc.contributor.authorPopoff, Alexander
dc.contributor.authorZaburannyi, Nestor
dc.contributor.authorZipf, Gregor
dc.contributor.authorMaier, Josef
dc.contributor.authorBernauer, Hubert S
dc.contributor.authorWenzel, Silke C
dc.contributor.authorMüller, Rolf
dc.date.accessioned2018-11-01T13:55:03Z
dc.date.available2018-11-01T13:55:03Z
dc.date.issued2018-10-14
dc.identifier.issn2041-6520
dc.identifier.pmid30319751
dc.identifier.doi10.1039/c8sc02046a
dc.identifier.urihttp://hdl.handle.net/10033/621529
dc.description.abstractSynthetic 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.en_US
dc.rightsAttribution-NonCommercial-ShareAlike 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/us/*
dc.titleSynthetic biology approaches and combinatorial biosynthesis towards heterologous lipopeptide production.en_US
dc.typeArticleen_US
dc.contributor.departmentHIPS, Helmholtz-Institut füt Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.en_US
refterms.dateFOA2018-11-01T13:55:03Z
dc.source.journaltitleChemical science


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