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深海放线菌 Nonomuraea sp. MM565M-173N2 来源的新型烯二炔类抗生素——海豹霉素。

Sealutomicins, new enediyne antibiotics from the deep-sea actinomycete Nonomuraea sp. MM565M-173N2.

机构信息

Institute of Microbial Chemistry (BIKAKEN), 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo, 141-0021, Japan.

Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, 4-2-1 Aoba-cho, Higashimurayama-shi, Tokyo, 189-0002, Japan.

出版信息

J Antibiot (Tokyo). 2021 May;74(5):291-299. doi: 10.1038/s41429-020-00402-1. Epub 2021 Feb 3.

Abstract

A Nonomuraea sp. strain MM565M-173N2 was isolated from deep-sea sediment off the Sanriku coast, and new antibiotics were evaluated against carbapenem-resistant Enterobacteriaceae (CRE), which is a problematic group of bacteria because of their antimicrobial resistance. From 220 l of fermented broth from strain MM565M-173N2, we isolated four new antibiotics by gel filtration and HPLC, designated as sealutomicins A (1.8 mg), B (1.5 mg), C (0.8 mg), and D (0.8 mg). Their structures were determined from MS, NMR, and CD spectra. Sealutomicin A was found to be a new enediyne antibiotic, while sealutomicins B-D were aromatized products from sealutomicin A. Sealutomicin A showed strong antibacterial activity (MIC 0.05-0.2 μg ml) against CRE.

摘要

一株丛毛单胞菌(Nonomuraea sp.)菌株 MM565M-173N2 从三陆海岸深海沉积物中分离得到,该菌株产生的新型抗生素可用于治疗碳青霉烯类耐药肠杆菌科(CRE)细菌,此类细菌因具有抗药性而成为一个严重的问题。从 MM565M-173N2 菌株的 220 升发酵液中,我们通过凝胶过滤和 HPLC 分离出四种新型抗生素,分别命名为 sealutomicin A(1.8mg)、B(1.5mg)、C(0.8mg)和 D(0.8mg)。通过 MS、NMR 和 CD 光谱确定了它们的结构。结果表明,sealutomicin A 是一种新型烯二炔类抗生素,而 sealutomicin B-D 则是 sealutomicin A 的芳构化产物。sealutomicin A 对 CRE 具有很强的抗菌活性(MIC0.05-0.2μg/ml)。

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