Biosynthesis of Mupirocin by Pseudomonas fluorescens NCIMB 10586 Involves Parallel Pathways

Shu-Shan Gao; Joanne Hothersall; Ji'en Wu; Annabel C. Murphy; Zhongshu Song; Elton R. Stephens; Christopher M. Thomas; Matthew P. Crump; Russell J. Cox; Thomas J. Simpson; Christine L. Willis

doi:10.1021/ja501731p

Biosynthesis of Mupirocin by Pseudomonas fluorescens NCIMB 10586 Involves Parallel Pathways

Shu-Shan Gao, Joanne Hothersall, Ji'en Wu, Annabel C. Murphy, Zhongshu Song, Elton R. Stephens, Christopher M. Thomas, Matthew P. Crump, Russell J. Cox, Thomas J. Simpson^*, Christine L. Willis

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

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Abstract

Mupirocin, a clinically important antibiotic produced via a trans-AT Type I polyketide synthase (PKS) in Pseudomonas fluorescens, consists of a mixture of mainly pseudomonic acids A, B, and C. Detailed metabolic profiling of mutant strains produced by systematic inactivation of PKS and tailoring genes, along with re-feeding of isolated metabolites to mutant stains, has allowed the isolation of a large number of novel metabolites, identification of the 10,11-epoxidase, and full characterization of the mupirocin biosynthetic pathway, which proceeds via major (10,11-epoxide) and minor (10,11-alkene) parallel pathways.

Original language	English
Pages (from-to)	5501-5507
Number of pages	7
Journal	Journal of the American Chemical Society
Volume	136
Issue number	14
DOIs	https://doi.org/10.1021/ja501731p
Publication status	Published - 9 Apr 2014

Research Groups and Themes

Bristol BioDesign Institute

Keywords

synthetic biology
ACYL CARRIER PROTEINS
REVEALS
GENE-CLUSTER
MUTATIONAL ANALYSIS
ACID-B
ANTIBIOTIC MUPIROCIN

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10.1021/ja501731p

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Revised: Engineering Trans-AT PKS antibiotic gene cluster to deliver bioactive compounds
Willis, C. L. (Principal Investigator)
31/07/14 → 31/03/22
Project: Research
3-month Core Capability for Chemistry Research
Crosby, J. (Principal Investigator)
1/01/13 → 1/04/13
Project: Research
CHEMICAL ANALYSIS OF HYBRID FUNGAL MEGASYNTHASES
Cox, R. J. (Principal Investigator)
1/10/08 → 1/10/12
Project: Research

Professor Matthew P Crump
- Matt.Crumpbristol.acuk
- School of Chemistry - Professor of NMR and Structural Biology
- Cancer
Person: Academic , Member
Professor Chris L Willis
- Chris.Willisbristol.acuk
- School of Chemistry - Professor of Organic Chemistry
Person: Academic

Cite this

@article{6c2ae42cecf44a6cbec9b4b415f973b5,

title = "Biosynthesis of Mupirocin by Pseudomonas fluorescens NCIMB 10586 Involves Parallel Pathways",

abstract = "Mupirocin, a clinically important antibiotic produced via a trans-AT Type I polyketide synthase (PKS) in Pseudomonas fluorescens, consists of a mixture of mainly pseudomonic acids A, B, and C. Detailed metabolic profiling of mutant strains produced by systematic inactivation of PKS and tailoring genes, along with re-feeding of isolated metabolites to mutant stains, has allowed the isolation of a large number of novel metabolites, identification of the 10,11-epoxidase, and full characterization of the mupirocin biosynthetic pathway, which proceeds via major (10,11-epoxide) and minor (10,11-alkene) parallel pathways.",

keywords = "synthetic biology, ACYL CARRIER PROTEINS, REVEALS, GENE-CLUSTER, MUTATIONAL ANALYSIS, ACID-B, ANTIBIOTIC MUPIROCIN",

author = "Shu-Shan Gao and Joanne Hothersall and Ji'en Wu and Murphy, {Annabel C.} and Zhongshu Song and Stephens, {Elton R.} and Thomas, {Christopher M.} and Crump, {Matthew P.} and Cox, {Russell J.} and Simpson, {Thomas J.} and Willis, {Christine L.}",

year = "2014",

month = apr,

day = "9",

doi = "10.1021/ja501731p",

language = "English",

volume = "136",

pages = "5501--5507",

journal = "Journal of the American Chemical Society",

issn = "0002-7863",

publisher = "American Chemical Society",

number = "14",

}

TY - JOUR

T1 - Biosynthesis of Mupirocin by Pseudomonas fluorescens NCIMB 10586 Involves Parallel Pathways

AU - Gao, Shu-Shan

AU - Hothersall, Joanne

AU - Wu, Ji'en

AU - Murphy, Annabel C.

AU - Song, Zhongshu

AU - Stephens, Elton R.

AU - Thomas, Christopher M.

AU - Crump, Matthew P.

AU - Cox, Russell J.

AU - Simpson, Thomas J.

AU - Willis, Christine L.

PY - 2014/4/9

Y1 - 2014/4/9

N2 - Mupirocin, a clinically important antibiotic produced via a trans-AT Type I polyketide synthase (PKS) in Pseudomonas fluorescens, consists of a mixture of mainly pseudomonic acids A, B, and C. Detailed metabolic profiling of mutant strains produced by systematic inactivation of PKS and tailoring genes, along with re-feeding of isolated metabolites to mutant stains, has allowed the isolation of a large number of novel metabolites, identification of the 10,11-epoxidase, and full characterization of the mupirocin biosynthetic pathway, which proceeds via major (10,11-epoxide) and minor (10,11-alkene) parallel pathways.

AB - Mupirocin, a clinically important antibiotic produced via a trans-AT Type I polyketide synthase (PKS) in Pseudomonas fluorescens, consists of a mixture of mainly pseudomonic acids A, B, and C. Detailed metabolic profiling of mutant strains produced by systematic inactivation of PKS and tailoring genes, along with re-feeding of isolated metabolites to mutant stains, has allowed the isolation of a large number of novel metabolites, identification of the 10,11-epoxidase, and full characterization of the mupirocin biosynthetic pathway, which proceeds via major (10,11-epoxide) and minor (10,11-alkene) parallel pathways.

KW - synthetic biology

KW - ACYL CARRIER PROTEINS

KW - REVEALS

KW - GENE-CLUSTER

KW - MUTATIONAL ANALYSIS

KW - ACID-B

KW - ANTIBIOTIC MUPIROCIN

U2 - 10.1021/ja501731p

DO - 10.1021/ja501731p

M3 - Article (Academic Journal)

C2 - 24625190

SN - 0002-7863

VL - 136

SP - 5501

EP - 5507

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

IS - 14

ER -

Biosynthesis of Mupirocin by Pseudomonas fluorescens NCIMB 10586 Involves Parallel Pathways

Abstract

Research Groups and Themes

Keywords

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Projects

Revised: Engineering Trans-AT PKS antibiotic gene cluster to deliver bioactive compounds

3-month Core Capability for Chemistry Research

CHEMICAL ANALYSIS OF HYBRID FUNGAL MEGASYNTHASES

Profiles

Professor Matthew P Crump

Professor Chris L Willis

Cite this