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)

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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

Keywords

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

Access to Document

10.1021/ja501731p

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1 Active
2 Finished

Revised: Engineering Trans-AT PKS antibiotic gene cluster to deliver bioactive compounds
Willis, C. L.
31/07/14 → 31/01/21
Project: Research
3-month Core Capability for Chemistry Research
Crosby, J.
1/01/13 → 1/04/13
Project: Research
CHEMICAL ANALYSIS OF HYBRID FUNGAL MEGASYNTHASES
Cox, R. J.
1/10/08 → 1/10/12
Project: Research

Professor Matthew P Crump
- Matt.Crump@bristol.ac.uk
- Fundamental Bioscience
- School of Chemistry - Professor of NMR and Structural Biology
- Cancer
- Biological and Archaeological Chemistry
- Spectroscopy and Dynamics
Person: Academic , Member
Professor Chris L Willis
- Chris.Willis@bristol.ac.uk
- Fundamental Bioscience
- Synthesis
- School of Chemistry - Professor of Organic Chemistry
- Catalysis
- Biological and Archaeological Chemistry
Person: Academic , Member

Cite this

Gao, Shu-Shan ; Hothersall, Joanne ; Wu, Ji'en ; Murphy, Annabel C. ; Song, Zhongshu ; Stephens, Elton R. ; Thomas, Christopher M. ; Crump, Matthew P. ; Cox, Russell J. ; Simpson, Thomas J. ; Willis, Christine L. / Biosynthesis of Mupirocin by Pseudomonas fluorescens NCIMB 10586 Involves Parallel Pathways. In: Journal of the American Chemical Society. 2014 ; Vol. 136, No. 14. pp. 5501-5507.

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

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",

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Biosynthesis of Mupirocin by Pseudomonas fluorescens NCIMB 10586 Involves Parallel Pathways. / Gao, Shu-Shan; Hothersall, Joanne; Wu, Ji'en; Murphy, Annabel C.; Song, Zhongshu; Stephens, Elton R.; Thomas, Christopher M.; Crump, Matthew P.; Cox, Russell J.; Simpson, Thomas J.; Willis, Christine L.

In: Journal of the American Chemical Society, Vol. 136, No. 14, 09.04.2014, p. 5501-5507.

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

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 - ACYL CARRIER PROTEINS

KW - ACID-B

KW - GENE-CLUSTER

KW - ANTIBIOTIC MUPIROCIN

KW - MUTATIONAL ANALYSIS

KW - REVEALS

U2 - 10.1021/ja501731p

DO - 10.1021/ja501731p

M3 - Article (Academic Journal)

C2 - 24625190

VL - 136

SP - 5501

EP - 5507

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

SN - 0002-7863

IS - 14

ER -

Biosynthesis of Mupirocin by Pseudomonas fluorescens NCIMB 10586 Involves Parallel Pathways

Abstract

Keywords

Access to Document

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

Professor Matthew P Crump

Professor Chris L Willis

Cite this