Abstract
Analysis of the genome sequence of Streptomyces sp. KCB13F003 showed the presence of a cryptic gene cluster encoding flavin-dependent halogenase and nonribosomal peptide synthetase. Pleiotropic approaches using multiple culture media followed by LC-MS-guided isolation and spectroscopic analysis enabled the identification of two new chlorinated cyclic hexapeptides, ulleungmycins A and B (1 and 2). Their structures, including absolute configurations, were determined by 1D and 2D NMR techniques, advanced Marfey's analysis, and GITC derivatization. The new peptides, featuring unusual amino acids 5-chloro-l-tryptophan and d-homoleucine, exhibited moderate antibacterial activities against Gram-positive pathogenic bacteria including methicillin-resistant and quinolone-resistant Staphylococcus aureus.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Anti-Bacterial Agents / chemistry
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Chromatography, Liquid
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Flavins / metabolism
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Genomics
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Gram-Positive Bacteria / drug effects
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Hydrocarbons, Chlorinated
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Methicillin Resistance / drug effects
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Methicillin-Resistant Staphylococcus aureus / drug effects
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Microbial Sensitivity Tests
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Molecular Structure
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Nuclear Magnetic Resonance, Biomolecular
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Oxidoreductases / metabolism
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Peptide Synthases / metabolism
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Peptides, Cyclic / chemistry
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Peptides, Cyclic / isolation & purification*
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Staphylococcal Infections
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Staphylococcus aureus / drug effects
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Streptomyces / chemistry*
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Streptomyces / genetics
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Tryptophan / metabolism
Substances
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Anti-Bacterial Agents
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Flavins
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Hydrocarbons, Chlorinated
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Peptides, Cyclic
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ulleungmycin A
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ulleungmycin B
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Tryptophan
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Oxidoreductases
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Peptide Synthases
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non-ribosomal peptide synthase