禾谷镰刀菌次级代谢产物研究  

Study on Secondary Metabolites from Fusarium graminearum

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作  者:张炳文 林雨琦 薛彦青 王婧 杨文超 王晓峰 刘文[2] Zhang Bingwen;Lin Yuqi;Xue Yanqing;Wang Jing;Yang Wenchao;Wang Xiaofeng;Liu Wen(School of Chemistry and Materials Science,Hangzhou Institute for Advanced Study,University of Chinese Academy of Sciences,Hangzhou 310024;State Key Laboratory of Bioorganic and Natural Products Chemistry,Shanghai Institute of Organic Chemistry,Chinese Academy of Sciences,Shanghai 200032;National Key Laboratory of Green Pesticide,Key Laboratory of Pesticide&Chemical Biology,Ministry of Education,Central China Normal University,Wuhan 430079)

机构地区:[1]国科大杭州高等研究院化学与材料科学学院,杭州310024 [2]中国科学院上海有机化学研究所生命有机化学国家重点实验室,上海200032 [3]华中师范大学化学学院农药与化学生物学教育部重点实验室,武汉430079

出  处:《有机化学》2023年第11期4003-4007,共5页Chinese Journal of Organic Chemistry

基  金:科技部重大专项(No.2022YFC2303100);国家自然科学基金(Nos.22193070,32030002);浙江省博士后科研择优资助项目。

摘  要:镰刀菌属真菌产多种次级代谢产物,且显示不同的生物功能.基于表观遗传学研究策略,敲除全局负调控因子kmt6基因,从而激活禾谷镰刀菌中常规培养条件下的沉默基因.接着对该突变株的次级代谢产物进行研究,从中分离鉴定了化合物1~4,其中fusarane B(1)和fusarane C(2)为新化合物.体外抗肿瘤活性实验表明,化合物1和3对宫颈癌细胞Hela和胰腺癌细胞Mia PaCa2两种人肿瘤细胞的生长有轻微的抑制活性.此外,结合体外测活和分子对接实验,对2个聚酮类化合物2和4的生物合成途径进行了推测.Fusarium species are able to produce structurally diverse secondary metabolites which exhibit different biological functions.Based on the epigenetic research strategy,the global negative regulator,kmt6 gene,which is related to the expression of the secondary metabolite gene cluster,was knocked out to activate the silent gene.A chemical investigation on the cultures extract of the mutant strain led to the isolation of compounds 1~4.Among them,fusarane B(1)and fusarane C(2)are two new compounds.Furthermore,the antitumor activities of 1~4 were assayed.Compounds 1 and 3 exhibited moderate inhibitory effect on two human cancer cells of Hela and Mia PaCa2.In addition,the biosynthetic pathways of two polyketones 2 and 4 were proposed based on in vivo examination and molecular docking experiment.

关 键 词:禾谷镰刀菌 次级代谢产物 抗肿瘤 生物合成 

分 类 号:Q93[生物学—微生物学]

 

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