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.
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High quality genome annotation and expression visualisation of a mupirocin-producing bacterium.
PLoS One
May 2022
School of Biosciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom.
Article Synopsis
- - Pseudomonas strain NCIMB10586 is capable of producing the antibiotic mupirocin and shows promise for industrial applications, with genomic studies underway to understand its genetics and physiology better.
- - Researchers improved the quality of the genome sequence by combining various sequencing methods, fixing numerous errors that affected key coding regions, and developed a detailed annotation pipeline.
- - RNA sequencing was conducted over 18 hours to analyze gene expression, revealing that mupirocin production peaks later in growth, while the resistance gene is consistently expressed throughout the growth period.
Defining the genes for the final steps in biosynthesis of the complex polyketide antibiotic mupirocin by Pseudomonas fluorescens NCIMB10586.
Sci Rep
February 2019
School of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
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.
View Article and Find Full Text PDFShift to Pseudomonic acid B production in P. fluorescens NCIMB10586 by mutation of mupirocin tailoring genes mupO, mupU, mupV, and macpE.
Chem Biol
July 2005
School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.
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.
View Article and Find Full Text PDFTandemly duplicated acyl carrier proteins, which increase polyketide antibiotic production, can apparently function either in parallel or in series.
J Biol Chem
February 2005
School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.
Polyketide biosynthesis involves the addition of subunits commonly derived from malonate or methylmalonate to a starter unit such as acetate. Type I polyketide synthases are multifunctional polypeptides that contain one or more modules, each of which normally contains all the enzymatic domains for a single round of extension and modification of the polyketide backbone. Acyl carrier proteins (ACP(s)) hold the extender unit to which the starter or growing chain is added.
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