Genomic analyses lead to novel secondary metabolites

被引：76

作者：

Banskota, Arjun H. ^{[1
]}

McAlpine, James B. ^{[1
]}

Sorensen, Dan ^{[1
]}

Ibrahim, Ashraf ^{[1
]}

Aouidate, Mustapha ^{[1
]}

Piraee, Mahmood ^{[1
]}

Alarco, Anne-Marie ^{[1
]}

Farnet, Chris M. ^{[1
]}

Zazopoulos, Emmanuel ^{[1
]}

机构：

[1] Ecopia BioSci Inc, Montreal, PQ H4S 2A1, Canada

来源：

JOURNAL OF ANTIBIOTICS | 2006年 / 59卷 / 09期

关键词：

amycolatopsis orientalis; ECO-0501; antibacterial; PKSI;

D O I：

10.1038/ja.2006.74

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 [微生物学]; 0836 [生物工程]; 090102 [作物遗传育种]; 100705 [微生物与生化药学];

摘要：

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 similar to 1c), N-acetylation (1d) and hydrogenation (le) in order to explore structure activity relationships (SAR).

引用

页码：533 / 542

页数：10

共 14 条

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