Genomic analyses lead to novel secondary metabolites

From National Research Council Canada

Alternative title	Genomic analyses lead to novel secondary metabolites. Part 3 ECO-0501, a novel antibacterial of a new class
DOI	Resolve DOI: https://doi.org/10.1038/ja.2006.74
Author	Search for: Banskota, Arjun H; Search for: McAlpine, James B; Search for: Sørensen, Dan; Search for: Ibrahim, Ashraf; Search for: Aouidate, Mustapha; Search for: Piraee, Mahmood; Search for: Alarco, Anne-Marie; Search for: Farnet, Chris M.; Search for: Zazopoulos, Emmanuel
Format	Text, Article
Subject	Amycolatopsis orientalis; ECO-0501; antibacterial; PKS I
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 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).
Publication date	2006-09-01
Language	English
Peer reviewed	Yes
NRC publication	This is a non-NRC publication "Non-NRC publications" are publications authored by NRC employees prior to their employment by NRC.
NPARC number	21274257
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Record identifier	4c8582c8-714f-4860-a66f-a231d87fde99
Record created	2015-03-06
Record modified	2020-04-22

Date modified:: 2024-10-28