Manipulation of quorum sensing regulation in Pseudomonas fluorescens NCIMB 10586 to increase mupirocin production

Joanne Hothersall, Annabel C. Murphy, Zafar Iqbal, Genevieve Campbell, Elton R. Stephens, Ji'en Wu, Helen Cooper, Steve Atkinson, Paul Williams, John Crosby, Christine L. Willis, Russell J. Cox, Thomas J. Simpson, Christopher M. Thomas

Research output: Contribution to journalArticle (Academic Journal)

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1017-1026
Number of pages10
JournalApplied Microbiology and Biotechnology
Volume90
Issue number3
DOIs
Publication statusPublished - May 2011

Projects

BIOSYNTHESIS OF POLYKETIDE ANTIBIOTIC MUPIROCIN BY PSEUDOMONAS FLUORESCENS

Simpson, T. J.

1/12/071/05/11

Project: Research

Cite this

Hothersall, J., Murphy, A. C., Iqbal, Z., Campbell, G., Stephens, E. R., Wu, J., Cooper, H., Atkinson, S., Williams, P., Crosby, J., Willis, C. L., Cox, R. J., Simpson, T. J., & Thomas, C. M. (2011). Manipulation of quorum sensing regulation in Pseudomonas fluorescens NCIMB 10586 to increase mupirocin production. Applied Microbiology and Biotechnology, 90(3), 1017-1026. https://doi.org/10.1007/s00253-011-3145-2