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dc.contributor.authorConnolly, Jack A.
dc.contributor.authorWilson, Amber
dc.contributor.authorMacioszek, Malgorzata
dc.contributor.authorSong, Zhongshu
dc.contributor.authorWang, Luoyi
dc.contributor.authorMohammad, Hadi H.
dc.contributor.authorYadav, Mukul
dc.contributor.authordi Martino, Maura
dc.contributor.authorMiller, Claire E.
dc.contributor.authorHothersall, Joanne
dc.contributor.authorHaines, Anthony S.
dc.contributor.authorStephens, Elton R.
dc.contributor.authorCrump, Matthew P.
dc.contributor.authorWillis, Christine L.
dc.contributor.authorSimpson, Thomas J.
dc.contributor.authorWinn, Peter J.
dc.contributor.authorThomas, Christopher M.
dc.date.accessioned2019-02-19T12:30:05Z
dc.date.available2019-02-19T12:30:05Z
dc.date.issued2019-02-07
dc.identifier.citationConnolly , J A , Wilson , A , Macioszek , M , Song , Z , Wang , L , Mohammad , H H , Yadav , M , di Martino , M , Miller , C E , Hothersall , J , Haines , A S , Stephens , E R , Crump , M P , Willis , C L , Simpson , T J , Winn , P J & Thomas , C M 2019 , ' Defining the genes for the final steps in biosynthesis of the complex polyketide antibiotic mupirocin by Pseudomonas fluorescens NCIMB10586 ' , Scientific Reports , vol. 9 , 1542 . https://doi.org/10.1038/s41598-018-38038-9en
dc.identifier.issn2045-2322
dc.identifier.otherPURE: 257793123
dc.identifier.otherPURE UUID: 500b24c0-18a0-4aa0-9878-ffd58725d449
dc.identifier.otherWOS: 000458017800010
dc.identifier.otherScopus: 85061280270
dc.identifier.otherWOS: 000458017800010
dc.identifier.urihttp://hdl.handle.net/10023/17095
dc.descriptionThis work was funded by BBSRC grants BB/I014373/1 and BB/I014039/1, by BBSRC and EPSRC through the Bristol Centre for Synthetic Biology (BB/L01386X) and NPRONET PoC10. JAC and MdiM were funded by BBSRC MIBTP (BB/J014532/1) studentships. MY was funded by an Indian State Scholarship. HHM was funded by an Iraqi Government Scholarship (HCED).en
dc.description.abstractThe mupirocin trans-AT polyketide synthase pathway, provides a model system for manipulation of antibiotic biosynthesis. Its final phase involves removal of the tertiary hydroxyl group from pseudomonic acid B, PA-B, producing the fully active PA-A in a complex series of steps. To further clarify requirements for this conversion, we fed extracts containing PA-B to mutants of the producer strain singly deficient in each mup gene. This additionally identified mupM and mupN as required plus the sequence but not enzymic activity of mupL and ruled out need for other mup genes. A plasmid expressing mupLMNOPVCFU + macpE together with a derivative of the producer P. fluorescens strain NCIMB10586 lacking the mup cluster allowed conversion of PA-B to PA-A. MupN converts apo-mAcpE to holo-form while MupM is a mupirocin-resistant isoleucyl tRNA synthase, preventing self-poisoning. Surprisingly, the expression plasmid failed to allow the closely related P. fluorescens strain SBW25 to convert PA-B to PA-A.
dc.format.extent9
dc.language.isoeng
dc.relation.ispartofScientific Reportsen
dc.rightsCopyright © The Author(s) 2019. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.en
dc.subjectQD Chemistryen
dc.subjectQH301 Biologyen
dc.subjectNDASen
dc.subject.lccQDen
dc.subject.lccQH301en
dc.titleDefining the genes for the final steps in biosynthesis of the complex polyketide antibiotic mupirocin by Pseudomonas fluorescens NCIMB10586en
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Chemistryen
dc.identifier.doihttps://doi.org/10.1038/s41598-018-38038-9
dc.description.statusPeer revieweden


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