蓝藻外代谢组的降脂活性和细胞毒性的筛选。
Screening of Lipid-Reducing Activity and Cytotoxicity of the Exometabolome from Cyanobacteria.
发表日期:2024 Sep 10
作者:
Rúben Luz, Rita Cordeiro, Vítor Gonçalves, Vitor Vasconcelos, Ralph Urbatzka
来源:
Marine Drugs
摘要:
蓝藻是次生代谢物的丰富生产者,将其中一些代谢物分泌到培养基中。然而,蓝藻外代谢组的研究很少,很少有研究关注其表征和生物活性评估。在这项工作中,通过 HR-ESI-LC-MS/MS 对 56 种蓝细菌菌株的外代谢组进行了表征。在两种癌细胞系 HepG2 和 HCT116 上评估了细胞毒性,同时在斑马鱼幼虫和脂肪酸超载的人肝细胞脂肪变性模型中测试了脂质的减少。使用 GNPS 进行的外代谢组分析揭示了几种菌株中许多复杂的独特化合物簇,但在公共数据库中没有识别。三种菌株降低了 HCT116 细胞的活力,即 Tolypotrichaceae BACA0428 (30.45%)、Aphanizomenonaceae BACA0025 (40.84%) 和 Microchaetaceae BACA0110 (46.61%)。仅通过暴露于杜西卡丝菌 sp. 观察到斑马鱼幼虫的脂质减少。 BACA0344 (60%)。基于特征的分子网络表明,这种生物活性与两种黄烷酮高度相关,这是文献中描述的具有降脂活性的化合物类别。蓝细菌菌株的外代谢组特征揭示了其高度的化学多样性,这支持其作为新型生物活性化合物的来源,尽管大多数时候被忽视。
Cyanobacteria are rich producers of secondary metabolites, excreting some of these to the culture media. However, the exometabolome of cyanobacteria has been poorly studied, and few studies have dwelled on its characterization and bioactivity assessment. In this work, exometabolomes of 56 cyanobacterial strains were characterized by HR-ESI-LC-MS/MS. Cytotoxicity was assessed on two carcinoma cell lines, HepG2 and HCT116, while the reduction in lipids was tested in zebrafish larvae and in a steatosis model with fatty acid-overloaded human liver cells. The exometabolome analysis using GNPS revealed many complex clusters of unique compounds in several strains, with no identifications in public databases. Three strains reduced viability in HCT116 cells, namely Tolypotrichaceae BACA0428 (30.45%), Aphanizomenonaceae BACA0025 (40.84%), and Microchaetaceae BACA0110 (46.61%). Lipid reduction in zebrafish larvae was only observed by exposure to Dulcicalothrix sp. BACA0344 (60%). The feature-based molecular network shows that this bioactivity was highly correlated with two flavanones, a compound class described in the literature to have lipid reduction activity. The exometabolome characterization of cyanobacteria strains revealed a high chemodiversity, which supports it as a source for novel bioactive compounds, despite most of the time being overlooked.