Shift to pseudomonic acid B production in P-fluorescens NCIMB10586 by mutation of Mupirocin tailoring genes mupO, mupV, and macpE

Research output: Contribution to journalArticle

Authors

  • Sian Cooper
  • W Laosripaiboon
  • AK El-Sayed
  • C Winfield
  • J Crosby
  • RJ Cox
  • TJ Simpson

Colleges, School and Institutes

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.

Details

Original languageEnglish
Pages (from-to)825-833
Number of pages9
JournalChemistry & Biology
Volume12
Issue number7
Publication statusPublished - 1 Jul 2005