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RK44 菌产生的信号分子和生物活性代谢产物。

Signalling and Bioactive Metabolites from sp. RK44.

机构信息

Marine Biodiscovery Centre, Department of Chemistry, University of Aberdeen, Meston Walk, Aberdeen AB24 3UE, Scotland AB24 3UE, UK.

College of Science, Department of Biology and Environmental Science, University of the Philippines Cebu, Lahug, Cebu 6000, Philippines.

出版信息

Molecules. 2020 Jan 22;25(3):460. doi: 10.3390/molecules25030460.

Abstract

remains one of the prolific sources of structural diversity, and a reservoir to mine for novel natural products. Continued screening for new Streptomyces strains in our laboratory led to the isolation of sp. RK44 from the underexplored areas of Kintampo waterfalls, Ghana, Africa. Preliminary screening of the metabolites from this strain resulted in the characterization of a new 2-alkyl-4-hydroxymethylfuran carboxamide (AHFA) together with five known compounds, cyclo-(L-Pro-Gly) , cyclo-(L-Pro-L-Phe) , cyclo-(L-Pro-L-Val) , cyclo-(L-Leu-Hyp) , and deferoxamine E AHFA , a methylenomycin (MMF) homolog exhibited anti-proliferative activity (EC = 89.6 µM) against melanoma A2058 cell lines. This activity, albeit weak is the first report amongst MMFs. Furthermore, the putative biosynthetic gene cluster () was identified for the biosynthesis of AHFA . DFO-E displayed potent anti-plasmodial activity (IC = 1.08µM) against 3D7. High-resolution electrospray ionization mass spectrometry (HR ESIMS) and molecular network assisted the targeted-isolation process, and tentatively identified six AHFA analogues, - and six siderophores -.

摘要

remains 是结构多样性的丰富来源之一,也是挖掘新型天然产物的宝库。我们实验室继续对新的链霉菌菌株进行筛选,从非洲加纳金坦博瀑布未充分探索的地区分离到了 sp. RK44。对该菌株代谢产物的初步筛选导致了一种新的 2-烷基-4-羟甲基呋喃甲酰胺 (AHFA) 的特征描述,以及另外五种已知化合物,环-(L-Pro-Gly)、环-(L-Pro-L-Phe)、环-(L-Pro-L-Val)、环-(L-Leu-Hyp)和去铁胺 E。AHFA 是一种甲基霉素 (MMF) 类似物,对黑色素瘤 A2058 细胞系表现出抗增殖活性(EC = 89.6 µM)。这种活性虽然较弱,但却是 MMFs 中的第一个报道。此外,还鉴定了 AHFA 生物合成的假定生物合成基因簇 ()。DFO-E 对 3D7 表现出很强的抗疟原虫活性(IC = 1.08µM)。高分辨率电喷雾电离质谱 (HR ESIMS) 和分子网络辅助了靶向分离过程,并暂定鉴定了六种 AHFA 类似物 - 和六种铁载体 -。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae13/7037778/5195e373b4f5/molecules-25-00460-g001.jpg

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