Defining the genes for the final steps in biosynthesis of the complex polyketide antibiotic mupirocin by Pseudomonas fluorescens NCIMB10586
MetadataShow full item record
The 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.
Connolly , 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/s41598-018-38038-9
Copyright © 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/.
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).
Items in the St Andrews Research Repository are protected by copyright, with all rights reserved, unless otherwise indicated.