Genomic analyses lead to novel secondary metabolites

Alternative titleGenomic analyses lead to novel secondary metabolites. Part 3 ECO-0501, a novel antibacterial of a new class
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DOIResolve DOI: http://doi.org/10.1038/ja.2006.74
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TypeArticle
ISSN0021-8820
1881-1469
Volume59
Issue9
Pages533542; # of pages: 10
SubjectAmycolatopsis orientalis; ECO-0501; antibacterial; PKS I
AbstractGenomic 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 1D 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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LanguageEnglish
Peer reviewedYes
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NPARC number21274257
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Record identifier4c8582c8-714f-4860-a66f-a231d87fde99
Record created2015-03-06
Record modified2016-05-09
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