Faculdade de Ciências e Tecnologia, Universidade dos Açores, 9500-321 Ponta Delgada, Portugal.
CIBIO, Centro de Investigação em Biodiversidade e Recursos Genéticos, InBIO Laboratório Associado, BIOPOLIS Program in Genomics, Biodiversity and Land Planning; UNESCO Chair-Land Within Sea: Biodiversity & Sustainability in Atlantic Islands, Universidade dos Açores, 9500-321 Ponta Delgada, Portugal.
Mar Drugs. 2024 Sep 10;22(9):412. doi: 10.3390/md22090412.
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 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.
蓝藻是次生代谢产物的丰富生产者，会将其中一些分泌到培养基中。然而，蓝藻的外代谢组学研究甚少，很少有研究深入研究其特征和生物活性评估。在这项工作中，通过 HR-ESI-LC-MS/MS 对 56 株蓝藻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，而在斑马鱼幼虫和脂肪酸超负荷的人肝细胞脂肪变性模型中测试了脂质减少情况。使用 GNPS 进行的外代谢组分析显示，在几种菌株中发现了许多独特化合物的复杂簇，在公共数据库中没有鉴定。三种菌株降低了 HCT116 细胞的活力，分别是 Tolypotrichaceae BACA0428（30.45%）、Aphanizomenonaceae BACA0025（40.84%）和 Microchaetaceae BACA0110（46.61%）。仅通过暴露于 sp. BACA0344 观察到斑马鱼幼虫中的脂质减少（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，黄烷酮是文献中描述具有脂质减少活性的一类化合物。蓝藻菌株的外代谢组学特征显示出高度的化学多样性，这支持它作为新型生物活性化合物的来源，尽管大多数时候都被忽视了。
