title: Shift to Pseudomonic acid B production in P. fluorescens NCIMB10586 by mutation of mupirocin tailoring genes mupO, mupU, mupV, and macpE.
abstract: Mupirocin, a polyketide-derived antibiotic from Pseudomonas fluorescens NCIMB10586, is a mixture of pseudomonic acids (PA) that target isoleucyl-tRNA synthase. The mup gene cluster encodes both type I polyketide synthases and monofunctional enzymes that should play a role during the conversion of the product of the polyketide synthase into the active antibiotic (tailoring). By in-frame deletion analysis of selected tailoring open-reading frames we show that mupQ, mupS, mupT, and mupW are essential for mupirocin production, whereas mupO, mupU, mupV, and macpE are essential for production of PA-A but not PA-B. Therefore, PA-B is not simply produced by hydroxylation of PA-A but is either a precursor of PA-A or a shunt product. In the mupW mutant, a new metabolite lacking the tetrahydropyran ring is produced, implicating mupW in oxidation of the 16-methyl group.
authors.affiliation: School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.
authors.forename: Sian M
authors.initials: SM
authors.lastname: Cooper
authors.forename: Wanpen
authors.initials: W
authors.lastname: Laosripaiboon
authors.forename: Ayesha S
authors.initials: AS
authors.lastname: Rahman
authors.forename: Joanne
authors.initials: J
authors.lastname: Hothersall
authors.forename: A Kassem
authors.initials: AK
authors.lastname: El-Sayed
authors.forename: Christopher
authors.initials: C
authors.lastname: Winfield
authors.forename: John
authors.initials: J
authors.lastname: Crosby
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* / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005227:Fatty Acids / Q000096:biosynthesis / Q000235:genetics; D007533:Isoleucine-tRNA Ligase / Q000235:genetics / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D005810:Multigene Family; D016712:Mupirocin / Q000031:analogs & derivatives / Q000378:metabolism*; D009154:Mutation; D016366:Open Reading Frames; D010084:Oxidation-Reduction; D048630:Polyketide Synthases / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011551:Pseudomonas fluorescens / Q000235:genetics / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D005227:Fatty Acids; D048630:Polyketide Synthases; C014246:pseudomonic acid I; D016712:Mupirocin; D007533:Isoleucine-tRNA Ligase