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从源自红树林的菌株SCSIO 40068中发现具有抗菌和细胞毒性活性的克班霉素

Discovery of Kebanmycins with Antibacterial and Cytotoxic Activities from the Mangrove-Derived sp. SCSIO 40068.

作者信息

Zhao Mengran, Zhang Wenjun, Yang Chunfang, Zhang Liping, Huang Huarong, Zhu Yiguang, Ratnasekera Disna, Zhang Changsheng

机构信息

Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China.

Sanya Institute of Ocean Eco-Environmental Engineering, Sanya 572000, China.

出版信息

J Nat Prod. 2024 Jun 28;87(6):1591-1600. doi: 10.1021/acs.jnatprod.4c00232. Epub 2024 Jun 11.

Abstract

Mangrove derived actinomycetes are a rich reservoir of bioactive natural products and play important roles in pharmaceutical chemistry. In a screen of actinomycetes from mangrove rhizosphere sedimental environments, the isolated strain sp. SCSIO 40068 displayed strong antibacterial activity. Further fractionation of the extract yielded four new compounds kebanmycins A-D (-) and two known analogues FD-594 () and the aglycon (). The structures of - were determined based on extensive spectroscopic data and single-crystal X-ray diffraction analysis. - featured a fused pyranonaphthaxanthene as an integral part of a 6/6/6/6/6/6 polycyclic motif, and showed bioactivity against a series of Gram-positive bacteria and cytotoxicity to several human tumor cells. In addition, the kebanmycins biosynthetic gene cluster () was identified in sp. SCSIO 40068, and KebMT2 was biochemically characterized as a tailoring sugar--methyltransferase, leading to a proposed biosynthetic route to -. This study paves the way to further investigate as a potential lead compound.

摘要

源自红树林的放线菌是生物活性天然产物的丰富来源,在药物化学中发挥着重要作用。在对红树林根际沉积环境中的放线菌进行筛选时,分离出的菌株sp. SCSIO 40068表现出很强的抗菌活性。对提取物进一步分级分离得到了四种新化合物克班霉素A-D(-)以及两种已知类似物FD-594()和苷元()。通过广泛的光谱数据和单晶X射线衍射分析确定了-的结构。-具有稠合的吡喃萘并蒽酮,是6/6/6/6/6/6多环基序的一个组成部分,对一系列革兰氏阳性细菌具有生物活性,对几种人类肿瘤细胞具有细胞毒性。此外,在sp. SCSIO 40068中鉴定出了克班霉素生物合成基因簇(),并且KebMT2被生化鉴定为一种修饰糖-O-甲基转移酶,从而提出了一条通往-的生物合成途径。这项研究为进一步研究作为潜在先导化合物铺平了道路。

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