Department of Chemistry, National Taiwan University, Taipei, 10617, Taiwan.
Department of Plant Pathology and Microbiology and Center for Biotechnology, National Taiwan University, Taipei, 10617, Taiwan.
Rapid Commun Mass Spectrom. 2020 Apr;34 Suppl 1:e8549. doi: 10.1002/rcm.8549. Epub 2019 Nov 6.
Natural products have been great sources for drug discovery. However, the structures of natural products are diverse and difficult to elucidate. Cordyceps militaris is a parasitic fungus which usually grows on host insects. The metabolites of C. militaris have been reported to act as chemotherapeutic agents. In this study, we aimed for the structural elucidation of specialized metabolites derived from C. militaris, and the metabolic impact in leukemia cells.
We describe a liquid chromatography data-dependent mass spectrometric platform combining tandem mass analysis and molecular networking. Leukemia cells treated with C. militaris extract and control groups were visualized in terms of their metabolic profiles using Global Natural Product Social (GNPS) molecular networking. By this method, we were able to elucidate the structures of metabolites from medicinal fungus extracts and cancer cells and then to recognize their changes in a semi-quantitative manner.
Using C. militaris and leukemia cells as examples, we found that approximately 100 new ion species were present in the treated leukemia cells, suggesting a highly altered metabolic profile. Specifically, based on the tandem mass spectral similarity, we proposed that cordycepin, a key fungus-derived therapeutic agent known for its antitumor activity, was transformed into its methylthio form in leukemia cells.
The platform described provides an ability to investigate complex molecular interactions of natural products in mammalian cells. By incorporating tandem mass spectrometry and molecular networking, we were able to reveal the chemical modification of crude bioactive compounds, for example potential bioactive compounds which might be modified from cordycepin. We envision that such a mass spectrometry (MS)-based workflow, combined with other metabolomics platforms, would enable much wider applicability to cell biology and be of great potential to pharmacological study as well as drug discovery.
天然产物一直是药物发现的重要来源。然而，天然产物的结构多样且难以阐明。蛹虫草是一种寄生真菌，通常生长在宿主昆虫上。蛹虫草的代谢产物已被报道具有化疗作用。在本研究中，我们旨在阐明来自蛹虫草的特征代谢产物的结构，并研究其对白血病细胞的代谢影响。
我们描述了一种液相色谱数据相关质谱平台，结合串联质谱分析和分子网络。使用全球天然产物社交网络（GNPS）分子网络，根据代谢谱观察用蛹虫草提取物处理和对照组的白血病细胞。通过这种方法，我们能够阐明药用真菌提取物和癌细胞中代谢物的结构，并以半定量的方式识别它们的变化。
以蛹虫草和白血病细胞为例，我们发现处理后的白血病细胞中存在约 100 种新的离子物质，表明代谢谱发生了高度改变。具体而言，基于串联质谱谱相似性，我们提出了一种假设，即虫草素是一种具有抗肿瘤活性的关键真菌来源的治疗剂，在白血病细胞中转化为其甲基硫代形式。
所描述的平台提供了研究天然产物在哺乳动物细胞中复杂分子相互作用的能力。通过结合串联质谱和分子网络，我们能够揭示粗生物活性化合物的化学修饰，例如可能从虫草素修饰而来的潜在生物活性化合物。我们设想，这种基于质谱（MS）的工作流程，结合其他代谢组学平台，将能够更广泛地应用于细胞生物学，并具有很大的药理学研究和药物发现潜力。
