基于质谱的分子网络分析化学调控对土曲霉C23-3次生代谢产物及生物活性的影响  

LC-MS/MS Based Molecular Network Analysis of the Effects of Chemical Regulation on the Secondary Metabolites and Biological Activities of a Fungal Strain Aspergillus terreus C23-3

作　　者：马小翔 刘亚月 聂影影 黎燕媚 王远 薛欣怡 洪鹏志 张翼 MA Xiao-xiang;LIU Ya-yue;NIE Ying-ying;LI Yan-mei;WANG Yuan;XUE Xin-yi;HONG Peng-zhi;ZHANG Yi(College of Food Science and Technology,Guangdong Ocean University,Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety,Guangdong Province Engineering Laboratory for Marine Biological Products,Guangdong Provincial Engineering Technology Research Center of Seafood,Key Laboratory of Advanced Processing of Aquatic Product of Guangdong Higher Education Institution,Zhanjiang Municipal Key Laboratory of Marine Drugs and Nutrition for Brain Health,Research Institute for Marine Drugs and Nutrition,Guangdong Ocean University,Zhanjiang 524088;Center for Marine Drugs Research&Development,Shenzhen Institute of Guangdong Ocean University,Shenzhen 518120;Collaborative Innovation Center of Seafood Deep Processing,Dalian Polytechnic University,Dalian 116034)

机构地区：[1]广东海洋大学食品科技学院广东省水产品加工与安全重点实验室广东省海洋生物制品工程实验室广东省海洋食品工程技术研究中心水产品深加工广东普通高等学校重点实验室湛江市脑健康海洋药物与营养品重点实验室广东海洋大学海洋药物研究所,湛江524088 [2]广东海洋大学深圳研究院海洋医药研发中心,深圳518120 [3]海洋食品精深加工关键技术省部共建协同创新中心大连工业大学,大连116034

出　　处：《生物技术通报》2021年第8期95-110,共16页Biotechnology Bulletin

基　　金：广东省扬帆计划引进紧缺拔尖人才项目(201433009);国家自然科学基金项目(21807015);深圳市科创委基础研究面上项目(JCYJ20190813105005619);深圳市大鹏新区产业发展资金(KY20180203);深圳市大鹏新区科技研发项目(KJYF202001-07);湛江市海洋经济创新发展示范市建设项目(湛海创XM-202008-01B1);广东省普通高校重点领域专项(生物医药与健康)(2021ZDZX2064)。

摘　　要：以一株高产丁内酯Ⅰ的海洋来源土曲霉C23-3作为出发菌株,筛选出可获得更丰富次生代谢产物的化学调控培养条件。利用2种基础培养基分别添加9种小分子化合物,对菌株进行24孔板上的化学调控培养,在菌丝体形态变化和薄层层析生物活性自显影基础上,运用液相色谱-串联质谱法以及基于质谱的分子网络进一步分析次生代谢产物的产量和多样性。在糙米培养基中分别加入金合欢醇(1 μmol/L)、法尼焦磷酸铵盐(FPP,5 μmol/L)、亚硫酸氢钠甲萘醌(MSB,10 μmol/L)、3-氨基-L-酪氨酸(1 mmol/L)等4种诱导条件均可调控菌株C23-3次级代谢产物发生较明显变化,其丁内酯、土震素和洛伐他汀类化合物的多样性和产量较为突出。菌株C23-3经化学调控后的次生代谢产物产生了不同程度的变化,为活性化合物的发现提供了基础。A marine-derived Aspergillus terreus strain C23-3 featuring of producing butyrolactone I was used as the starting strain to screen out chemically regulative cultural conditions under which abundant secondary metabolites can be produced.The strain was cultured on 24-well plates under chemically regulative conditions established by two types of basic media supplied with 9 small molecule compounds respectively.Based on the changes of mycelial morphology and the thin layer chromatography bioautography,the liquid chromatography-tandem mass spectrometry and the MS based molecular networking were used to further analyze the yield and diversity of secondary metabolites.Four chemical inducing conditions,e.g.,brown rice medium supplied with(E,E)-farnesol(1μmol/L),farnesyl pyrophosphate ammonium salt(5μmol/L),menadione sodium bisulfite(10μmol/L),or 3-amino-l-tyrosine(1 mmol/L)induced remarkable changes of secondary metabolites,especially with prominent diversity and yield of butyrolactones,territrems and lovastatin derivatives.The secondary metabolites of strain C23-3 have changed to different extents after chemical regulation,which provides a basis for the discovery of active compounds.

关 键 词：海洋真菌 化学调控 丁内酯 LC-MS/MS 分子网络 

分 类 号：Q936[生物学—微生物学]