PTP1B抑制活性真菌F956的鉴定和代谢产物研究  

Identification of fungus F956 and its metabolites with PTP1B inhibitory activity

作　　者：霍培元[1] 徐岩[1] 林洁[1] 李业英[1] 郑海洲[1] 沈文斌 任晓[1] 石英[1] 崔晓兰[1] 郑智慧[1] 路新华[1] 张雪霞[1] 

机构地区：[1]微生物药物国家工程研究中心河北省工业微生物代谢工程技术研究中心华北制药集团新药研究开发有限责任公司,石家庄050015

出　　处：《中国抗生素杂志》2018年第1期35-39,共5页Chinese Journal of Antibiotics

基　　金：河北省科技条件建设项目(No.169676404G)

摘　　要：目的研究PTP1B抑制活性真菌菌株F956及其代谢产物。方法通过形态观察及ITS序列系统发育分析鉴定活性菌株F956;对其发酵产物进行分离纯化获得单体化合物并通过综合波谱解析确定代谢产物的化学结构。对得到的化合物进行分子对接及PTP1B抑制活性评价。结果 F956鉴定为Mucor fragilis(易脆毛霉);从其代谢产物中得到2个具有PTP1B抑制活性的化合物F956-5和F956-6,其中F956-5与化合物JBIR-12相同,F956-6为JBIR-12的13位羟基甲基化衍生物,分子对接结果显示F956-6可占据PTP1B的活性位点;其对PTP1B的IC_(50)分别为7.12和13.92μg/mL。结论化合物F956-5(JBIR-12)和F956-6由易脆毛霉产生及其对PTP1B的抑制活性均为首次报道。Objective To identify a filamentous strain F956 and study the activity of its metabolites. Methods The strain was identified by the cultural and morphological characteristics and phylogenetic analysis based on ITS rDNA; Active constituents were isolated and purified by various chromatographic techniques and the chemical structures were elucidated on the basis of comprehensive spectral data analysis. The inhibition of the compounds to PTP1B and molecular docking were evaluated. Results The strain F956 was identified as Mucorfragilis. Two compounds F956-5 and F956-6 were isolated from the metabolites. F956-5 was the same as compound JBIR- 12. F956-6 was a new compound. Molecular docking showed F956-6 could occupy the active site of PTP1B. They exhibited significant inhibition to PTPIB with ICs0 values of 7.12 and 13.92μg/mL. Conclusion F956-5（JBIR-12） and F956-6 were isolated from Mucorfragilis firstly and reported as specific PTP1B inhibitors for the first time.

关 键 词：真菌 易脆毛霉 ITS序列分析 PTP1B抑制剂 

分 类 号：R915[医药卫生—微生物与生化药学]