Biosynthesis of Mupirocin by Pseudomonas fluorescens NCIMB 10586 Involves Parallel Pathways

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 gen...

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Bibliographic Details
Published in:Journal of the American Chemical Society 2014-04, Vol.136 (14), p.5501-5507
Main Authors: 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
Format: Article
Language:English
Subjects:
Molecular Conformation
Mupirocin - biosynthesis
Mupirocin - chemistry
Polyketide Synthases - genetics
Polyketide Synthases - metabolism
Pseudomonas fluorescens - enzymology
Pseudomonas fluorescens - metabolism
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Summary: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.
ISSN:0002-7863
1520-5126
DOI:10.1021/ja501731p