海洋链霉菌IMB3-202产生的吲哚咔唑生物碱

Identification of indolocarbazoles from the marine-derived Streptomyces sp.IMB3-202

目的分离鉴定海洋链霉菌IMB3-202产生的抗菌和抗肿瘤活性产物。方法利用Anti SMASH对菌株基因组进行生物信息学分析;运用多种色谱手段分离纯化IMB3-202的活性产物;通过波谱学方法鉴定化合物的化学结构;采用微量肉汤稀释法和MTT法分别测定化合物的抗菌和细胞毒活性。结果菌株IMB3-202基因组含有一条吲哚咔唑类生物合成基因簇。通过发酵条件优化,从中分离鉴定了4个吲哚咔唑类化合物,结构分别确定为星形孢菌素、3'-O-去甲基星形孢菌素、holyrine A和K252c。星形孢菌素、3'-O-去甲基星形孢菌素和holyrine A对HeLa细胞、HCT116和MCF-7等肿瘤细胞具有很强的抑制活性,IC_(50)值为0.75~1192.8 nmol/L。星形孢菌素对金黄色葡萄球菌和白色念珠菌显示出较弱的抗菌活性,最低抑菌浓度值为128μg/ml。结论通过基因组序列分析,可以在基因水平上预测产物结构,快速识别特定类型产物。

Objective To identify the antibacterial and cytotoxic products from the marine-derived Streptomyces sp.IMB3-202.Methods The potential biosynthetic gene clusters were analyzed using antiSMASH 3.0.The metabolites from Streptomyces sp.IMB3-202 were isolated and purified by a combination of various chromotographic techniques.The structures were elucidated by spectroscopic analysis.The antibacterial and cytotoxic activities of the products were evaluated by using broth micro-dilution and MTT methods,respectively.Results The bioinformatic analysis revealed that the geome of strain IMB3-202 contained a gene cluster highly homologous to the known indolocarbazole biosynthetic gene cluster.Four indolocarbazole analogues were obtained.Their structures were identified as staurosporine(1),3'-O-demethylstaurosporine(2),holyrine A(3)and K252c(4).Compounds 1-3 displayed potent cytotoxicity against human HeLa,HCT116,and MCF-7 cancer cell lines with IC50 values ranging from 0.75 to 1192.8 nmol/L.Compound 1 showed weak antibacterial activity against Staphylococcus aureus and Candida albicans(MIC:128μg/ml).Conclusion Four indolocarbazole analogues were obtained from the marine-derived Streptomyces sp.IMB3-202 by genomic analysis.