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Prealamethicin F50 and related peptaibols from Trichoderma arundinaceum: validation of their authenticity via in situ chemical analysis

机译:阿曼木霉中的Prealamethicin F50和相关肽段:通过原位化学分析验证其真实性

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In the field of natural products chemistry, a common question pertains to the authenticity of an isolated compound, i.e. are the interesting side chains biosynthesized naturally or an artefact of the isolation/purification processes? The droplet-liquid microjunction-surface sampling probe (droplet-LMJ-SSP) coupled to a hyphenated system (UPLC-UV-HRESIMS) empowers the analysis of natural product sources in situ, providing data on the biosynthetic timing and spatial distribution of secondary metabolites. In this study the droplet-LMJ-SSP was utilized to validate the authenticity of two new peptaibols (2 and 3) as biosynthesized secondary metabolites, even though both of them had structural features that could be perceived as artefacts. Compounds 2 and 3 were isolated from the scaled up fermentation of Trichoderma arundinaceum (strain MSX70741), along with a new member of the trichobrevin BIII complex (1), and four known compounds (4–7). The structures of the isolates were established using a set of spectroscopic and spectrometric methods, and their absolute configurations were determined by Marfey's analysis. The cytotoxic activity of compounds 1, 3, 4 and 6 was evaluated against a panel of cancer cell lines, where cytotoxic activity in the single digit μM range was observed.
机译:在天然产物化学领域,一个常见的问题与分离出的化合物的真实性有关,即天然合成的有趣侧链还是分离/纯化过程的人工产物?液滴-液体微结表面采样探针(droplet-LMJ-SSP)与连字系统(UPLC-UV-HRESIMS)耦合,可对天然产物来源进行原位分析,提供生物合成数据次生代谢产物的时间和空间分布。在这项研究中,液滴-LMJ-SSP被用来验证两种新的肽醇(2和3)作为生物合成的次生代谢产物的真实性,即使它们两者都具有可以被视为伪影的结构特征。化合物2和3是从木霉(Trichoderma arundinaceum)(菌株MSX70741)的大规模发酵中分离出来的,以及新的Trichobrevin BIII复合物成员(1)和四个已知化合物(4-7)。分离物的结构是使用一套光谱学和光谱学方法建立的,其绝对构型是通过Marfey分析确定的。针对一组癌细胞系评估了化合物1、3、4和6的细胞毒活性,在其中观察到的细胞毒活性在个位数μM范围内。

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