title: Manipulation of quorum sensing regulation in Pseudomonas fluorescens NCIMB 10586 to increase mupirocin production.
abstract: Transcription of the 74 kb Pseudomonas fluorescens mupirocin [pseudomonic acid (PA)] biosynthesis cluster depends on quorum sensing-dependent regulation via the LuxI/LuxR homologues MupI/MupR. To facilitate analysis of novel PAs from pathway mutants, we investigated factors that affect mup gene expression. First, the signal produced by MupI was identified as N-(3-oxodecanoyl)homoserine lactone, but exogenous addition of this molecule did not activate mupirocin production prematurely nor did expression of mupI in trans increase metabolite production. Second, we confirmed that mupX, encoding an amidase/hydrolase that can degrade N-acylhomoserine lactones, is also required for efficient expression, consistent with its occurrence in a regulatory module linked to unrelated genes in P. fluorescens. Third, and most significantly, mupR expression in trans to wild type and mutants can increase production of antibiotic and novel intermediates up to 17-fold.
authors.affiliation: School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
authors.forename: Joanne
authors.initials: J
authors.lastname: Hothersall
authors.forename: Annabel C
authors.initials: AC
authors.lastname: Murphy
authors.forename: Zafar
authors.initials: Z
authors.lastname: Iqbal
authors.forename: Genevieve
authors.initials: G
authors.lastname: Campbell
authors.forename: Elton R
authors.initials: ER
authors.lastname: Stephens
authors.forename: Ji'en
authors.initials: J
authors.lastname: Wu
authors.forename: Helen
authors.initials: H
authors.lastname: Cooper
authors.forename: Steve
authors.initials: S
authors.lastname: Atkinson
authors.forename: Paul
authors.initials: P
authors.lastname: Williams
authors.forename: John
authors.initials: J
authors.lastname: Crosby
authors.forename: Christine L
authors.initials: CL
authors.lastname: Willis
authors.forename: Russell J
authors.initials: RJ
authors.lastname: Cox
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Simpson
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Thomas
mesh_terms: D000900:Anti-Bacterial Agents / Q000096:biosynthesis; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D016712:Mupirocin / Q000378:metabolism*; D011551:Pseudomonas fluorescens / Q000235:genetics / Q000502:physiology*; D053038:Quorum Sensing; D015854:Up-Regulation
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D016712:Mupirocin