Supercritical Fluid Extraction Enhances Discovery of Secondary Metabolites from Myxobacteria
Supercritical Fluid Extraction Enhances Discovery of Secondary Metabolites from Myxobacteria
复制标题
超临界流体萃取技术促进粘细菌次级代谢产物的发现
DOI：
10.1021/acs.analchem.0c02995
复制
发表时间：
2020-12-01
影响因子：
7.4
通讯作者：
Mueller, Rolf
中科院分区：
文献类型：
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作者：
Bader, Chantal D.;Neuber, Markus;Mueller, Rolf
超临界流体萃取(SFE)被广泛用于从植物中分离天然产物，但它在鉴定结构和物理化学上经常是不同的微生物天然产物方面的应用迄今为止是有限的。在本研究中，我们评估了超临界流体萃取对粘细菌次生代谢物萃取率的影响，旨在提高发现新天然产物的前景。我们考察了不同共溶剂对三株粘细菌次生代谢物提取效率的影响以及相应提取物的抗菌活性。对于每一种已知的次生代谢物，我们发现使用超临界流体萃取法的提取条件与传统的溶剂萃取法相比，萃取物的得率更高。当以20%乙酸乙酯为共溶剂时，IOGP大于3的化合物的萃取率最高，而当使用更多的极性共溶剂(如甲醇)时，logP小于3的化合物的萃取率最高。用SFE产生的提取物显示出更强的抗菌活性，包括存在已知粘菌次生代谢物无法解释的活性，突出了SFE在生物活性导向分离方面的优势。此外，非靶向代谢组学分析揭示了一组由研究较好的模型粘细菌粘液黄色葡萄球菌DK1622产生的氯代谢物，这些代谢物以前由于常规提取物中浓度较低而无法获得。将浓缩的SF提取物用于氯黄原酸A的分离和结构鉴定，该化合物是一个新的次生代谢物家族的创始成员。我们的发现鼓励将超临界流体萃取作为未来微生物天然产品筛选工作流程的一部分来增加利用。
Supercritical fluid extraction (SFE) is widely used for the isolation of natural products from plants, but its application in efforts to identify structurally and physicochemically often dissimilar microbial natural products is limited to date. In this study, we evaluated the impact of SFE on the extractability of myxobacterial secondary metabolites, aiming to improve the prospects of discovering novel natural products. We investigated the influence of different co-solvents on the extraction efficiency of secondary metabolites from three myxobacterial strains and the antimicrobial activity profiles of the corresponding extracts. For each known secondary metabolite, we found extraction conditions using SFE leading to superior yields in the extracts compared to conventional solvent extraction. Compounds with a IogP higher than 3 showed the best extraction efficiency using 20% EtOAc as a co-solvent, whereas compounds with logP values lower than 3 were better extractable using more polar co-solvents such as MeOH. Extracts generated with SFE showed increased antimicrobial activities including the presence of activities not explained by known myxobacterial secondary metabolites, highlighting the advantage of SFE for bioactivity-guided isolation. Moreover, non-targeted metabolomics analysis revealed a group of chlorinated metabolites produced by the well-studied model myxobacterium Myxococcus xanthus DK1622, which were not accessible previously due to their low concentration in conventional extracts. The enriched SF extracts were used for isolation and subsequent structure elucidation of chloroxanthic acid A as the founding member of a novel secondary metabolite family. Our findings encourage the increased utilization of SFE as a part of future screening workflows of microbial natural products.