AI Article Synopsis
- Genomic analysis of Amycolatopsis orientalis ATCC 43491 shows it can produce at least 10 secondary metabolites beyond vancomycin, including a new glycosidic polyketide called ECO-0501.
- Screening culture extracts confirmed the presence of ECO-0501, which was structurally validated through various spectral analyses.
- ECO-0501 showed potent antibacterial activity against multiple drug-resistant Gram-positive bacteria and was chemically modified to investigate its structure-activity relationships.
Article Abstract
Genomic analyses of Amycolatopsis orientalis ATCC 43491 strain, deposited as a vancomycin producer, revealed the presence of genetic loci for the production of at least 10 secondary metabolites other than vancomycin. One of these gene clusters, which contained a type I polyketide synthase, was predicted to direct the synthesis of novel class of compound, a glycosidic polyketide ECO-0501 (1). Screening of culture extracts for a compound with the predicted physicochemical properties of the product from this locus, led to the isolation of the 13-O-glucuronide of 13-hydroxy-2,12,14,16,22-pentamethyl-28-(N-methyl-guanidino)-octacosa-2,4,6,8,10,14,20,24-octaenoic acid (2-hydroxy-5-oxo-cyclopent-1-enyl)-amide (ECO-0501, 1). The structure, confirmed by spectral analyses including MS, and ID and 2D NMR experiments, were in accord with that predicted by genomic analyses. ECO-0501 possessed strong antibacterial activity against a series of Gram-positive pathogens including several strains of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE). ECO-0501 was chemically modified by esterification (1a-1c), N-acetylation (1d) and hydrogenation (1e) in order to explore structure activity relationships (SAR).
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| http://dx.doi.org/10.1038/ja.2006.74 | DOI Listing |
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