College of Pharmacy, Guizhou University, Guiyang 550025, P.R. China.
Southwest Biomedical Resources of the Ministry of Education, Guizhou University, Guiyang 550025, P.R. China.
Can J Microbiol. 2022 Aug 1;68(8):531-541. doi: 10.1139/cjm-2022-0067. Epub 2022 Jun 1.
The special niche of endophytic fungi promotes their potential to produce antitumor compounds with novel structure and significant bioactivity for screening of new antitumor drugs. In our previous studies, we isolated a strain from the roots of the medicinal plant and identified it as . We found that the crude extract of had significant antitumor activity on A549 cancer cells, and overexpressing the global regulatory factor FnVeA (the gene of the fungus ) resulted in a significant increase in the antitumor activity, which was approximately fivefold higher than wild strain for relative inhibition rate. In , the accumulation of indole, alkene, alkaloid, steroid, and flavonoid metabolites with potential antitumor activity was significantly upregulated compared with wild type via metabolomic analysis. Moreover, the transcriptome analysis showed that 134 differential genes were considered to be closely related to the biosynthesis of antitumor substances, of which 59 differential genes were considered as candidate key genes, and related to tryptophan dimethylallyltransferase, cytochrome P450 monooxygenase, polyketide synthases, and transcription factors. Taken together, we suggest that FnVeA may regulate the biosynthesis of antitumor substances by mediating the expression of genes related to secondary metabolic pathways in .
内生真菌的特殊生态位促进了其产生具有新颖结构和显著生物活性的抗肿瘤化合物的潜力，可用于筛选新型抗肿瘤药物。在我们之前的研究中，我们从药用植物的根部分离出一株 ，并将其鉴定为 。我们发现 的粗提物对 A549 癌细胞具有显著的抗肿瘤活性，过表达全局调控因子 FnVeA（真菌的 基因）导致抗肿瘤活性显著增加，相对抑制率约为野生型的五倍。通过代谢组学分析，发现与野生型相比， 中具有潜在抗肿瘤活性的吲哚、烯烃、生物碱、甾体和类黄酮代谢物的积累显著上调。此外，转录组分析表明，有 134 个差异基因被认为与抗肿瘤物质的生物合成密切相关，其中 59 个差异基因被认为是候选关键基因，与色氨酸二甲基烯丙基转移酶、细胞色素 P450 单加氧酶、聚酮合酶和转录因子有关。综上所述，我们认为 FnVeA 可能通过调节与次级代谢途径相关的基因表达来调节 中抗肿瘤物质的生物合成。
