Zhang Shikai, Xu Qing, Ji Changbo, Han Xiaoyu, Zhou Yang, Liang Chao, Ma Linran, Sun Weijian, Li Yanling, Yang Zhengyou, Zhao Fengchun, Tian Yuan
Department of Microbiology, College of Life Science, Key Laboratory for Agriculture Microbiology, Shandong Agricultural University, Taian, China.
College of Life Science, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, China.
Front Microbiol. 2023 Oct 9;14:1254609. doi: 10.3389/fmicb.2023.1254609. eCollection 2023.
Small molecule-induced fermentation of the endophytic fungus sp. AC1 originated from was executed to investigate its secondary metabolites. It was fermented in a culture medium containing 5-hydroxytryptophan (5-HTP), 1-methyl-L-tryptophan (1-MT), and tryptamine (TA), respectively. The antibacterial activities of crude extracts against pathogenic bacteria and pathogenic fungi were determined by using the Oxford cup method, while the cytotoxicity of crude extracts against cancer cells was determined by using the MTT method. The results showed that the secondary metabolites of sp. AC1 induced by 1-MT exhibited optimal antibacterial activity and tumor cytotoxicity. The induction conditions of 1-MT were optimized, and the antibacterial activities and tumor cytotoxicity of crude extracts under different induction conditions were investigated. As indicated, the optimal moment for 1-MT addition was before inoculation and its optimal concentration was 0.25 mM. Under these conditions, sp. AC1 was fermented and approximately 12 g of crude extracts was obtained. The crude extracts were then separated and purified to acquire nine monomer compounds, including three new compounds (-) and six known compounds (-). The antibacterial activities of the compounds against pathogenic bacteria and pathogenic fungi were investigated by using the microdilution method, while their cytotoxicity against cancer cells was analyzed by using the MTT method. The results demonstrated that Compound exhibited moderate antibacterial activities against , and , as well as a low inhibitory activity against . Nevertheless, Compound showed significant cytotoxicity against five cancer cells, with IC ranging from 12.26 to 52.52 μM. Compounds and exhibited negligible biological activity, while other compounds showed detectable inhibitory activities against pathogenic bacteria and cancer cells.
对源自内生真菌sp. AC1的小分子诱导发酵进行了研究，以探究其次级代谢产物。分别在含有5-羟色氨酸（5-HTP）、1-甲基-L-色氨酸（1-MT）和色胺（TA）的培养基中进行发酵。采用牛津杯法测定粗提物对病原菌和致病真菌的抗菌活性，采用MTT法测定粗提物对癌细胞的细胞毒性。结果表明，1-MT诱导的sp. AC1的次级代谢产物表现出最佳的抗菌活性和肿瘤细胞毒性。对1-MT的诱导条件进行了优化，并研究了不同诱导条件下粗提物的抗菌活性和肿瘤细胞毒性。结果表明，添加1-MT的最佳时机是接种前，其最佳浓度为0.25 mM。在此条件下，对sp. AC1进行发酵，获得了约12 g粗提物。然后对粗提物进行分离纯化，得到9种单体化合物，包括3种新化合物（-）和6种已知化合物（-）。采用微量稀释法研究了这些化合物对病原菌和致病真菌的抗菌活性，采用MTT法分析了它们对癌细胞的细胞毒性。结果表明，化合物对、和表现出中等抗菌活性，对表现出低抑制活性。然而，化合物对5种癌细胞表现出显著的细胞毒性，IC范围为12.26至52.52 μM。化合物和表现出可忽略不计的生物活性，而其他化合物对病原菌和癌细胞表现出可检测到的抑制活性。
