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Biosynthesis of mupirocin by Pseudomonas fluorescens NCIMB 10586 involves parallel pathways
Shu-Shan Gao1, Joanne Hothersall, Ji'en Wu
1School of Chemistry, University of Bristol , Bristol BS8 1TS, U.K.
Journal of the American Chemical Society
|March 15, 2014
Summary
This study details the mupirocin biosynthesis pathway in Pseudomonas fluorescens. Researchers identified novel metabolites and key enzymes, revealing parallel pathways for this important antibiotic.
Area of Science:
- Microbiology
- Biochemistry
- Synthetic biology
Background:
- Mupirocin is a crucial antibiotic produced by Pseudomonas fluorescens.
- Its production involves a trans-AT Type I polyketide synthase (PKS).
- The antibiotic is a mixture of pseudomonic acids A, B, and C.
Purpose of the Study:
- To fully characterize the mupirocin biosynthetic pathway.
- To identify novel metabolites and key enzymes involved in its production.
- To understand the parallel pathways of mupirocin biosynthesis.
Main Methods:
- Metabolic profiling of genetically modified Pseudomonas fluorescens strains.
- Systematic inactivation of polyketide synthase (PKS) and tailoring genes.
- Re-feeding of isolated metabolites to mutant strains.
Main Results:
- Isolation of numerous novel metabolites.
- Identification of the 10,11-epoxidase enzyme.
- Characterization of the mupirocin pathway proceeding via major (epoxide) and minor (alkene) parallel routes.
Conclusions:
- The mupirocin biosynthetic pathway is fully elucidated.
- Novel metabolites and the 10,11-epoxidase are key components.
- Understanding these pathways offers insights for antibiotic production.
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