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Genetic Engineering in Streptomyces roseosporus to Produce Hybrid Lipopeptide Antibiotics
- Source :
- Chemistry & Biology. 13:269-276
- Publication Year :
- 2006
- Publisher :
- Elsevier BV, 2006.
-
Abstract
- SummaryDaptomycin is a lipopeptide antibiotic produced by a nonribosomal peptide synthetase (NRPS) in Streptomyces roseosporus. The holoenzyme is composed of three subunits, encoded by the dptA, dptBC, and dptD genes, each responsible for incorporating particular amino acids into the peptide. We introduced expression plasmids carrying dptD or NRPS genes encoding subunits from two related lipopeptide biosynthetic pathways into a daptomycin nonproducing strain of S. roseosporus harboring a deletion of dptD. All constructs successfully complemented the deletion in trans, generating three peptide cores related to daptomycin. When these were coupled with incomplete methylation of 1 amino acid and natural variation in the lipid side chain, 18 lipopeptides were generated. Substantial amounts of nine of these compounds were readily obtained by fermentation, and all displayed antibacterial activity against gram-positive pathogens.
- Subjects :
- MICROBIO
Streptomyces roseosporus
Lipoproteins
Molecular Sequence Data
Clinical Biochemistry
Peptide
Biology
Methylation
Biochemistry
Streptomyces
Microbiology
chemistry.chemical_compound
Daptomycin
Nonribosomal peptide
Drug Discovery
medicine
Amino Acid Sequence
Cloning, Molecular
Peptide Synthases
Molecular Biology
Peptide sequence
Gram-Positive Bacterial Infections
Pharmacology
chemistry.chemical_classification
Base Sequence
Lipopeptide
General Medicine
biology.organism_classification
Anti-Bacterial Agents
Amino acid
Protein Subunits
chemistry
Multigene Family
Molecular Medicine
Genetic Engineering
Plasmids
medicine.drug
Subjects
Details
- ISSN :
- 10745521
- Volume :
- 13
- Database :
- OpenAIRE
- Journal :
- Chemistry & Biology
- Accession number :
- edsair.doi.dedup.....bd5959da5dd832b37b8f00bbc3dbb6fe