基于代谢组学探究表观遗传调控对老鼠簕内生真菌抗卵巢癌代谢物的影响  

Using metabolomics to explore the effects of epigenetic-modification strategies on the metabolites of Acanthus ilicifolius L.endophytic fungi against ovarian cancer

作　　者：麻晓琳 蔡来燕 刘妍颖 幸尚平 康亮 韦霞 朱丹 MA Xiaolin;CAI Laiyan;LIU Yanying;XING Shangping;KANG Liang;WEI Xia;ZHU Dan(Pharmaceutical College,Guangxi Medical University,Nanning 530021,China;Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation,Nanning 530021,China;Department of Pharmacy,the Second Affiliated Hospital,Guangxi Medical University,Nanning 530007,China)

机构地区：[1]广西医科大学药学院,广西南宁530021 [2]广西生物活性分子研究与评价重点实验室,广西南宁530021 [3]广西医科大学第二附属医院药学部,广西南宁530007

出　　处：《色谱》2024年第11期1015-1023,共9页Chinese Journal of Chromatography

基　　金：国家自然科学基金(82160734);广西科技重大专项(桂科AA22096021);广西重点研发计划(桂科AB21196048);广西中药材品质创新研究团队(GZKJ2305);大学生创新创业训练项目(202410598031).

摘　　要：本研究旨在探究表观遗传修饰策略对老鼠簕内生真菌Diaporthe goulteri产生抗卵巢癌代谢物的影响。研究以抗卵巢癌活性为指标,采用CCK-8(cell counting kit-8)方法筛选粗提物的活性,控制发酵时间、修饰剂种类和浓度等变量,进而采用超高效液相色谱-质谱联用方法进行非靶向代谢组学分析,通过主成分分析和正交偏最小二乘判别分析,构建了多变量统计分析模型,结合模型和变量重要性投影(VIP),使用Massbank数据库进行定性,筛选并鉴定出15种在控制组与修饰组之间具有显著性差异的代谢物(VIP≥1,P<0.05),主要包括聚酮类、氨基酸及衍生物类、生物碱类与有机酸类化合物等,其中10种物质含量上调,5种物质含量下调。研究结合了抗卵巢癌活性筛选与代谢组学分析,旨在发现潜在的活性代谢物,为红树植物老鼠簕资源的深入开发和活性化合物的靶向分离提供了科学依据。Ovarian cancer is a serious threat to women’s health and safety.So far,people have discovered more than 130 small molecule compounds of natural origin for anti-tumor,of which approximately 50%are of microbial origin.The Acanthus ilicifolius L.species is primarily distributed in the Guangdong,Hainan,and Guangxi regions of China and grows in tidally accessible coastal areas.Recent studies have revealed that Acanthus ilicifolius L.extracts are endowed with a range of pharmacological properties,including anti-inflammatory,hepatoprotective,antioxidant,and antitumor activities.Endophytic fungi are commonly found in the healthy tissue and organs of medicinal plants.These fungi and the plants they inhabit form mutually beneficial symbiotic relationships.Endophytic fungi produce a series of secondary metabolites,with active substances having shown great economic value and applications prospects in drug research and development as well as for the biological control of plant diseases.Secondary metabolites production by endophytic fungi is regulated by specific gene clusters,and several techniques have been used to stimulate the secondary metabolic processes of fungi,including epigenetic-modification and OSMAC(one strain many compounds)strategies,co-culturing,and gene modification.Among these,epigenetic modification has been shown to be effective;this strategy involves the addition of small-molecule epigenetic modifiers to the culture medium,thereby activating silenced biosynthetic gene clusters without altering the DNA sequences of the fungi.This approach facilitates the expression of silenced genes in endophytic fungi,thereby increasing the number and diversity of secondary metabolites.Furthermore,it assists in overcoming the inhibition of microbial secondary-metabolite synthesis under laboratory conditions,and enhances silenced-gene expressions.The advent of novel analytical techniques and bioinformatics has provided a comprehensive, multifaceted, and holistic understanding of fungal metabolism through the development o

关 键 词：液相色谱-质谱 内生真菌 抗卵巢癌活性 表观遗传修饰 代谢组学 

分 类 号：O658[理学—分析化学]