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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.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 .
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.relation.ispartofScientific Reportsen
dc.subjectQD Chemistryen
dc.subjectQH301 Biologyen
dc.titleDefining the genes for the final steps in biosynthesis of the complex polyketide antibiotic mupirocin by Pseudomonas fluorescens NCIMB10586en
dc.typeJournal articleen
dc.contributor.institutionUniversity of St Andrews. School of Chemistryen
dc.description.statusPeer revieweden

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