Abstract
Hybrid genome-mining/15N-NMR was used to target compounds containing piperazate (Piz) residues, leading to the discovery of caveamides A (1) and B (2) from Streptomyces sp. strain BE230, isolated from New Rankin Cave (Missouri). Caveamides are highly dynamic molecules containing an unprecedented β-ketoamide polyketide fragment, two Piz residues, and a new N-methyl-cyclohexenylalanine residue. Caveamide B (2) exhibited nanomolar cytotoxicity against several cancer cell lines and nanomolar antimicrobial activity against MRSA and E. coli.
MeSH terms
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Alanine / analogs & derivatives
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Alanine / chemistry
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Alanine / pharmacology
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Anti-Bacterial Agents / chemistry
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Anti-Bacterial Agents / isolation & purification
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Anti-Bacterial Agents / pharmacology
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / isolation & purification
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Antineoplastic Agents / pharmacology
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Cell Line, Tumor
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Drug Screening Assays, Antitumor
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Escherichia coli* / drug effects
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Humans
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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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Peptides / chemistry
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Peptides / isolation & purification
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Peptides / pharmacology
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Pyridazines
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Streptomyces* / chemistry