Title of article :
Shift to Pseudomonic Acid B Production in P. fluorescens NCIMB10586 by Mutation of Mupirocin Tailoring Genes mupO, mupU, mupV, and macpE Original Research Article
Author/Authors :
Sian M. Cooper، نويسنده , , Wanpen Laosripaiboon، نويسنده , , Ayesha S. Rahman، نويسنده , , Joanne Hothersall، نويسنده , , A. Kassem El-Sayed، نويسنده , , Christopher Winfield، نويسنده , , John Crosby and Matthew P. Crump، نويسنده , , Russell J. Cox، نويسنده , , Thomas J. Simpson، نويسنده , , Christopher M. Thomas، نويسنده ,
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.
