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

doi:10.13560/j.cnki.biotech.bull.1985.2020-1398

生物技术通报 ›› 2021, Vol. 37 ›› Issue (8): 95-110.doi: 10.13560/j.cnki.biotech.bull.1985.2020-1398

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

马小翔¹(), 刘亚月¹^,²^,³, 聂影影², 黎燕媚¹, 王远¹, 薛欣怡¹, 洪鹏志¹^,²^,³, 张翼¹^,²^,³()

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

收稿日期:2020-11-18 出版日期:2021-08-26 发布日期:2021-09-10
作者简介:马小翔,女,硕士研究生,研究方向：海洋天然产物;E-mail： ma.xiao.xiang@163.com
基金资助:
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)

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

MA Xiao-xiang¹(), LIU Ya-yue¹^,²^,³, NIE Ying-ying², LI Yan-mei¹, WANG Yuan¹, XUE Xin-yi¹, HONG Peng-zhi¹^,²^,³, ZHANG Yi¹^,²^,³()

1. 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
2. Center for Marine Drugs Research & Development,Shenzhen Institute of Guangdong Ocean University,Shenzhen 518120
3. Collaborative Innovation Center of Seafood Deep Processing,Dalian Polytechnic University,Dalian 116034

Received:2020-11-18 Published:2021-08-26 Online:2021-09-10

摘要/Abstract

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。

关键词: 海洋真菌, 化学调控, 丁内酯, LC-MS/MS, 分子网络

Abstract:

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（1 µmol/L）,farnesyl pyrophosphate ammonium salt（5 μmol/L）,menadione sodium bisulfite（10 µmol/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.

Key words: marine fungus, chemical regulation, butyrolactone, LC-MS/MS, molecular networking

马小翔, 刘亚月, 聂影影, 黎燕媚, 王远, 薛欣怡, 洪鹏志, 张翼. 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[J]. 生物技术通报, 2021, 37(8): 95-110.

MA Xiao-xiang, LIU Ya-yue, NIE Ying-ying, LI Yan-mei, WANG Yuan, XUE Xin-yi, HONG Peng-zhi, ZHANG Yi. 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[J]. Biotechnology Bulletin, 2021, 37(8): 95-110.

图/表 9

图1 菌株C23-3化学调控前后生长形态（培养28 d） A：左侧为海水马铃薯液体培养基,右侧为糙米培养基;从上至下分别是添加了3-氨基-L-酪氨酸、3-羟基-L-酪氨酸、3-硝基-L-酪氨酸、3,4-二羟基苯丙酮酸、金合欢醇、亚硫酸氢钠甲萘醌（MSB）和过氧化氢（H2O2）的实验组。B：上方为海水马铃薯液体培养基,下方为糙米培养基;左侧3列为添加了法尼焦磷酸铵盐（FPP）的实验组,最右1列为添加了L-硒代蛋氨酸的实验组。C：上方为海水马铃薯液体培养基,下方为糙米培养基;从左至右分别是添加了无菌水、DMSO和5%HCl的溶剂对照组以及空白对照组. 图片下方标记为加入诱导剂的浓度。上述每组两个平行

Fig.1 Growth morphology of strain C23-3 before and after chemical regulation（cultured for 28 days） A：The left column shows the cultures in seawater potato liquid medium,and the right column is for brown rice medium;the photos from top to bottom are experimental groups added 3-amino-L-tyrosine,3-hydroxy-L-tyrosine,3-nitro-L-tyrosine,3,4-dihydroxyphenylpyruvate,farnesol,MSB and H2O2,respectively. B：The top is for the seawater potato liquid medium,and the bottom is for the brown rice medium;the 3 columns on the left are the experimental groups with FPP,and the last column on the right is the experimental group with L-selenomethionine. C：The top is for the seawater potato liquid medium,and the bottom is for the brown rice medium;the photos from left to right are the solvent control groups supplemented with sterile water,DMSO and 5% HCl and blank control groups. The labels below the picture are the concentrations of the inducers added. For each of the above groups,two repeats were set

表1 化学调控前后的菌株C23-3代谢产物TLC指纹图谱比较

Table 1 The comparison of TLC fingerprints of strain C23-3 metabolic products before and after chemical regulation

实验组/空白组和试剂对照组 Experimental group vs. blank group and reagent control group	变化组分的R_f值范围 R_f value ranges of variant components	波长 Wavelength 254 nm	波长 Wavelength 365 nm	茴香醛显色 Anisaldehyde colorization	DPPH自由基清除活性DPPH free radical scavenging activity	铁氰化钾-三氯化铁显色K₃[Fe（CN）₆]-FeCl₃ colorization	乙酰胆碱酯酶抑制活性（R_f 0.67-0.90）Acetylcholinesterase inhibitory activity（R_f 0.67-0.90）
3-氨基-L-酪氨酸（1 mmol/L）组/空白组和5%HCl组 3-Amino-L-tyrosine（1 mmol/L）group vs. blank group and 5%HCl group	0.14-0.50	-	+	-	+	+	+
3-羟基-L-酪氨酸（10 mmol/L）组/空白组和5%HCl组 3-Hydroxy-L-tyrosine（10 mmol/L）group vs. blank group and 5%HCl group	0.11-0.46	+	+	-	+	+	+
3-硝基-L-酪氨酸（10 mmol/L）组/空白组和5%HCl组 3-Nitro-L-tyrosine（10 mmol/L）group vs. blank group and 5%HCl group	0.17-0.53	/	+	+	+	+	+
FPP（5 µmol/L）组/空白组 FPP（5 µmol/L）group vs. blank group	0.16-0.55	-	/	+	/	/	+
3,4-二羟基苯丙酮酸（1 mmol/L）组/空白组和DMSO组 3,4-Dihydroxyphenylpyruvate（1 mmol/L）group vs. blank group and DMSO group	0.16-0.53	+	+	/	+	+	+
金合欢醇（1 µmol/L）组/空白组和DMSO组 Farnesol（1 µmol/L）group vs. blank group and DMSO group	0.15-0.53	+	+	/	+	/	+
MSB（10 µmol/L）组/空白组和无菌水组MSB（10 µmol/L）group vs. blank group and sterile water group	0.13-0.45	/	/	/	+	+	/
H₂O₂（1 mmol/L）组/空白组和无菌水组（14 d）H₂O_2（1 mmol/L）group vs. blank group and sterile water group（14 d）	0.20-0.53	/	/	/	+	+	/
L-硒代蛋氨酸（61 mmol/L）组/空白组和无菌水组 L-selenomethionine（61 mmol/L）group vs. blank group and sterile water group	0.15-0.38	/	+	/	/	+	/

表1 化学调控前后的菌株C23-3代谢产物TLC指纹图谱比较

Table 1 The comparison of TLC fingerprints of strain C23-3 metabolic products before and after chemical regulation

实验组/空白组和试剂对照组 Experimental group vs. blank group and reagent control group	变化组分的R_f值范围 R_f value ranges of variant components	波长 Wavelength 254 nm	波长 Wavelength 365 nm	茴香醛显色 Anisaldehyde colorization	DPPH自由基清除活性DPPH free radical scavenging activity	铁氰化钾-三氯化铁显色K₃[Fe（CN）₆]-FeCl₃ colorization	乙酰胆碱酯酶抑制活性（R_f 0.67-0.90）Acetylcholinesterase inhibitory activity（R_f 0.67-0.90）
3-氨基-L-酪氨酸（1 mmol/L）组/空白组和5%HCl组 3-Amino-L-tyrosine（1 mmol/L）group vs. blank group and 5%HCl group	0.14-0.50	-	+	-	+	+	+
3-羟基-L-酪氨酸（10 mmol/L）组/空白组和5%HCl组 3-Hydroxy-L-tyrosine（10 mmol/L）group vs. blank group and 5%HCl group	0.11-0.46	+	+	-	+	+	+
3-硝基-L-酪氨酸（10 mmol/L）组/空白组和5%HCl组 3-Nitro-L-tyrosine（10 mmol/L）group vs. blank group and 5%HCl group	0.17-0.53	/	+	+	+	+	+
FPP（5 µmol/L）组/空白组 FPP（5 µmol/L）group vs. blank group	0.16-0.55	-	/	+	/	/	+
3,4-二羟基苯丙酮酸（1 mmol/L）组/空白组和DMSO组 3,4-Dihydroxyphenylpyruvate（1 mmol/L）group vs. blank group and DMSO group	0.16-0.53	+	+	/	+	+	+
金合欢醇（1 µmol/L）组/空白组和DMSO组 Farnesol（1 µmol/L）group vs. blank group and DMSO group	0.15-0.53	+	+	/	+	/	+
MSB（10 µmol/L）组/空白组和无菌水组MSB（10 µmol/L）group vs. blank group and sterile water group	0.13-0.45	/	/	/	+	+	/
H₂O₂（1 mmol/L）组/空白组和无菌水组（14 d）H₂O_2（1 mmol/L）group vs. blank group and sterile water group（14 d）	0.20-0.53	/	/	/	+	+	/
L-硒代蛋氨酸（61 mmol/L）组/空白组和无菌水组 L-selenomethionine（61 mmol/L）group vs. blank group and sterile water group	0.15-0.38	/	+	/	/	+	/

图2 菌株 C23-3 化学调控前后发酵产物 TLC 指纹图谱（糙米培养基） A1-C1：254 nm 紫外图像;A2-C2：365 nm 荧光图像;A3-C3：茴香醛硫酸显色;A4-C4：1,1-二苯基-2-三硝基苯肼（1,1-Diphenyl-2-picryl-hydrazyl,DPPH）自由基清除活性自显影;A5-C5：铁氰化钾-三氯化铁显色;A6-C6：乙酰胆碱酯酶抑制活性自显影。缩写：FPP：法尼焦磷酸铵盐、MSB：亚硫酸氢钠甲萘醌

Fig.2 TLC fingerprints of strain C23-3 fermentation products before and after chemical regulation（brown rice medium） A1-C1：UV images under 254 nm;A2-C2：fluorescence images under 365 nm;A3-C3：images of colorization by anisaldehyde-sulfuric acid reagent;A4-C4：images of 1,1-Diphenyl-2-picryl-hydrazyl（DPPH）free radical scavenging bioautography;A5-C5：images of colorization by potassium ferricyanide-ferric chloride reagent;A6-C6：images of acetylcholinesterase inhibitory bioautography. Abbreviations：Farnesyl pyrophosphate ammonium salt to FPP,menadione sodium bisulfite to MSB

图3 菌株C23-3不同培养条件下代谢产物基于二级质谱联系的分子网络图及局部放大图 A1及A2：化合物丁内酯Ⅰ的同类物离子簇放大图;B：化合物土震素B的同类物离子簇放大图;C：洛伐他汀的同类物离子簇放大图。Compounds 1-4：分别是丁内酯Ⅰ、土震素B、洛伐他汀、洛伐他汀羟酸;Compounds 5-13：已知化合物的可能衍生物,分别是[M（丁内酯Ⅰ异构体）+H]+,[M（丁内酯Ⅰ-2H）+H]+,[M（丁内酯Ⅰ异构体+O）+H]+,[M（丁内酯Ⅰ-H2O）+H]+,[M（土震素B-O）+H]+,[M（土震素B-CH2）+H]+,[M（洛伐他汀-H2O）+H]+,[M（洛伐他汀-O）+H]+,[M（洛伐他汀+2H）+H]+。分子网络图中的节点包含15种颜色, 分别表示化合物的15个样品来源：依次是分别添加了3-氨基-L-酪氨酸（1 mmol/L）、3-羟基-L-酪氨酸（10 mmol/L）、3-硝基-L-酪氨酸（10 mmol/L）、3,4-二羟基苯丙酮酸（1 mmol/L）、金合欢醇（1 µmol/L）、法尼焦磷酸铵盐（5 μmol/L）、亚硫酸氢钠甲萘醌（10 µmol/L）、H2O2（1 mmol/L）和硒代蛋氨酸（61 mmol/L）的诱导组;培养了14 d、28 d的空白组;分别添加了5%HCl、DMSO、无菌水的试剂对照组（其中无菌水组培养14 d、28 d）

Fig.3 Molecular network and its partial enlarged diagram of the metabolites of strain C23-3 under different cultural condi-tions based on MS2 relationships A1 and A2：Enlarged images of ion clusters of butyrolactone I congeners;B：enlarged images of ion clusters of territrem B congeners;C：enlarged images of ion clusters of lovastatin congeners. Compounds 1-4：butyrolactone I,territrem B,lovastatin,and lovastatin hydroxy acid. Compounds 5-13：Possible derivatives of known compounds,i.e.,[M（butyrolactoneⅠisomer）+H]+,[M（butyrolactoneⅠ-2H）+H]+,[M（butyrolactoneⅠisomer+O）+H]+,[M（butyrolactone I-H2O）+H]+,[M（territrem B-O）+H]+,[M（territrem B-CH2）+H]+,[M（lovastatin-H2O）+H]+,[M（lovastatin-O）+H]+,and[M（lovastatin+2H）+H]+,respectively. The nodes in the molecular network are marked in 15 colors, ,sequentially representing the 15 sample sources of compounds：induction groups with the addition of 3-amino-L-tyrosine（1 mmol/L）,3-hydroxy-L-tyrosine（10 mmol/L）,3-nitro-L-tyrosine（10 mmol/L）,3,4-dihydroxyphenylpyruvate（1 mmol/L）,farnesol（1 µmol/L）,FPP（5 μmol/L）,MSB（10 µmol/L）,H2O2（1 mmol /L）and selenomethionine（61 mmol/L）;blank groups cultured for 14 d and 28 d;reagent control groups supplemented separately with 5% HCl,DMSO,and sterile water（the sterile water group cultures for 14 d and 28 d,respectively）

图4 菌株C23-3不同培养条件下代谢产物的液质联用基峰色谱图 A-C分别为添加有小分子前体酪氨酸/4-羟基苯丙酮酸的类似物（3-氨基-L-酪氨酸、3-羟基-L-酪氨酸、3-硝基-L-酪氨酸和3,4-二羟基苯丙酮酸）、氧化胁迫剂（亚硫酸氢钠甲萘醌（MSB）和H2O2）、L-硒代蛋氨酸、天然萜类侧链供体二甲基烯丙基二磷酸的类似物（法尼焦磷酸铵盐（FPP）和金合欢醇）的诱导组及其对应的空白组和溶剂对照组的液质基峰色谱图。除了特殊说明“14 d”的组为培养14 d的提取物,其他均为培养28 d。组别名称标注在每个基峰色谱图的左上角。黑框标注的是丁内酯Ⅰ,蓝框标注的是土震素B,紫框标记的是洛伐他汀,绿框标记的是洛伐他汀羟酸;箭头标注的是有变化的代谢产物

Fig.4 Base peak chromatograms of the metabolites of strain C23-3 under different culture conditions A-C are the LC-MS base peak chromatograms of the induction groups added with analogs of small molecule precursor tyrosine/4-hydroxyphenylpyruvate（3-amino-L-tyrosine,3-hydroxy-L-tyrosine,3-nitro -L-tyrosine and 3,4-dihydroxyphenylpyruvate）,oxidative stress agents MSB and H2O2）,L-selenomethionine,and analogs of natural terpenoid side chain donor dimethylallyl diphosphate FPPand farnesol）,their corresponding blank groups and solvent control groups. Except for the specified “14 d” groups,which are for the 14 d culture extracts,the other groups were cultured for 28 d. The group name is marked in the upper left corner of each base peak chromatogram. The black frames label butyrolactone I,the blue ones label territrem B,the purple ones label lovastatin,and the green ones label lovastatin hydroxy acid;the arrows indicate variant metabolites

图5 Compound 1及其可能衍生物的二级质谱图 Compounds 1和5-8的标注同图3中化合物编号。相似度表示样品中检测到的化合物与GNPS数据库中的纯化合物或与GNPS分子网络注释的已知化合物compound 1或compound 5二级质谱的相似性比较的cosine值（图5红圈标记的是二者对应的系列碎片离子）。（本图及后文图6-图7中母离子的质荷比与图3分子网络相应节点的质荷比有小于0.5 Da的误差,是因为分子网络中节点标注的是一组质谱图中母离子质荷比的平均值,而图5-图7中来自其中具体的某张质谱）。Compound 5在分子网络图中没有与丁内酯Ⅰ匹配上,无cosine值,但通过二级质谱的人工比对,推测其可能是丁内酯Ⅰ的异构体

Fig. 5 MS2 spectra of compound 1 and its possible derivatives The labeling of Compounds 1 and 5-8 follows the same numbers as in Fig.3. The similarity values represent the cosine values of the similarity comparison between detected compounds in samples and the pure compounds recorded in GNPS database or the annotated known compound 1 or compound 5 by GNPS molecular networking（the red circles in Fig.5 mark the corresponding series of fragment ions tween the two compared compounds）.（The m/z values of the parent ions in this figure and the following Fig.6 and Fig.7,showed small errors less than 0.5 Da compared with the values of the corresponding nodes in Fig.3. This difference was produced because the m/z values marked on the nodes in the molecular network are the average m/z values of the precursor ions in a set of mass spectra,and the values in Figs.5-7 are specific values from specific mass spectra）. Compound 5 does not match with butyrolactone I in the molecular network and has no cosine value. However,it is speculated to be an isomer of butyrolactone I through the manual comparison of MS2 spectra

图6 Compound 2及其可能衍生物的二级质谱图 Compounds 2和9-10的标注同图3中化合物编号

Fig.6 MS2 spectra of compound 2 and its possible derivatives The labeling of compound 2 and 9-10 follows the same numbers as in Fig.3

图7 Compounds 3、4及其可能衍生物的二级质谱图 Compounds 3、4和11-13的标注同图3中化合物编号

Fig.7 MS2 spectra of compounds 3,4 and their possible derivatives The labeling of compounds 3,4 and 11-13 follows the same numbers as in Fig.3

图8 菌株C23-3不同化学调控条件下的代谢物中特征产物及其衍生物的含量 1-9组：分别添加了3-氨基-L-酪氨酸（1 mmol/L）、3-羟基-L-酪氨酸（10 mmol/L）、3-硝基-L-酪氨酸（10 mmol/L）、法尼焦磷酸铵盐FPP（5 μmol/L）、3,4-二羟基苯丙酮酸（1 mmol/L）、金合欢醇（1 µmol/L）、亚硫酸氢钠甲萘醌MSB（10 µmol/L）、H2O2（1 mmol/L）和L-硒代蛋氨酸（61 mmol/L）的诱导组。Compounds 1-13的标注同图3。峰面积（area）的单位为counts,counts = CPS*s

Fig.8 Contents of the characteristic products and their derivatives in the metabolites of strain C23-3 under different chemically regulated conditions Groups 1-9：Induction groups added with 3-amino-L-tyrosine（1 mmol/L）,3-hydroxy-L-tyrosine（10 mmol/L）,3-nitro-L-tyrosine（10 mmol/L）,FPP（5 μmol/L）,3,4-dihydroxyphenylpyruvate（1 mmol/L）,farnesol（1 µmol/L）,MSB（10 µmol /L）,H2O2（1 mmol/L）,and L-selenomethionine（61 mmol/L）respectively. The labeling of compounds 1-13 follows the same numbers as in Fig.3. The unit of peak area（area）is counts,counts = CPS*s

参考文献 27

[1]	张偲, 张长生, 田新朋, 等. 中国海洋微生物多样性研究[J]. 生物多样性保护, 2010, 25(6):652-658.
	Zhang S, Zhang CS, Tian XP, et al. The study of diversities of marine microbes in China[J]. Biodiversity Conservation, 2010, 25(6):652-658.
[2]	Blunt JW, Carroll AR, Copp BR, et al. Marine natural products[J]. Natural Product Reports, 2018, 35(1):8-53. doi: 10.1039/c7np00052a pmid: 29335692
[3]	Newman DJ, Cragg GM. Natural products as sources of new drugs over the 30 years from 1981 to 2010[J]. Journal of Natural Products, 2012, 75(3):311-335. doi: 10.1021/np200906s pmid: 22316239
[4]	赵成英, 朱统汉, 朱伟明. 2010~2013之海洋微生物新天然产物[J]. 有机化学, 2013, 33(6):1195-1234.
	Zhao CY, Zhu TH, Zhu WM. New marine natural products of microbial origin from 2010 to 2013[J]. Chinese Journal of Organic Chemistry, 2013, 33(6):1195-1234.
[5]	Keller NP. Fungal secondary metabolism:regulation, function and drug discovery[J]. Nature Reviews Microbiology, 2019, 17(3):167-180. doi: 10.1038/s41579-018-0121-1 pmid: 30531948
[6]	Bode HB, Bethe B, Höfs R, et al. Big effects from small changes:possible ways to explore nature’s chemical diversity[J]. ChemBioChem, 2002, 3(7):619-627. doi: 10.1002/1439-7633(20020703)3:7<619::AID-CBIC619>3.0.CO;2-9 URL
[7]	Yang JY, Sanchez LM, Rath CM, et al. Molecular networking as a dereplication strategy[J]. Journal of Natural Products, 2013, 76(9):1686-1699. doi: 10.1021/np400413s URL
[8]	Wang M, Carver JJ, Phelan VV, et al. Sharing and community curation of mass spectrometry data with global natural products social molecular networking[J]. Nature Biotechnology, 2016, 34(8):828-837. doi: 10.1038/nbt.3597 URL
[9]	Nie YY, Yang WC, Liu YY, et al. Acetylcholinesterase inhibitors and antioxidants mining from marine fungi:bioassays, bioactivity coupled LC-MS/MS analyses and molecular networking[J]. Marine Life Science & Technology, 2020, 2(4):386-397.
[10]	梁金月, 李文卿, 杨静明, 等. 海洋土曲霉C23-3与不同类型海洋微生物共培养对其次生代谢产物的影响[J]. 广东海洋大学学报, 2020, 40(1):44-54.
	Liang JY, Li WQ, Yang JM, et al. Effects of co-culture of marine fungus Aspergillus terreus C23-3 and different types of marine microorganisms on secondary metabolites[J]. Journal of Guangdong Ocean University, 2020, 40(1):44-54.
[11]	Haroon MH, Premaratne SR, Choudhry MI, et al. A new β-glucuronidase inhibiting butyrolactone from the marine endophytic fungus Aspergillus terreus[J]. Natural Product Research, 2013, 27(12):1060-1066. doi: 10.1080/14786419.2012.708659 pmid: 22913423
[12]	Ma XH, Zhu TJ, Gu QQ, et al. Structures and Antiviral Activities of Butyrolactone Derivatives Isolated from Aspergillus terreus MXH-23[J]. Journal of Ocean University of China, 2014, 13(6):1067-1070. doi: 10.1007/s11802-014-2324-z URL
[13]	Ibrahim SRM, Mohamed GA, Khedr AIM. γ-Butyrolactones from Aspergillus species:structures, biosynjournal, and biological activities[J]. Natural Product Communications, 2017, 12(5):791-800. pmid: 30496667
[14]	Quintanilla RA, Orellana DI, González-Billault C, et al. Interleukin-6 induces Alzheimer-type phosphorylation of tau protein by deregulating the cdk5/p35 pathway[J]. Experimental Cell Research, 2004, 295(1):245-57. pmid: 15051507
[15]	Wei W, Wang X, Kusiak J W. Signaling events in amyloid β-peptide-induced neuronal death and insulin-like growth factor I protection[J]. Journal of Biological Chemistry, 2002, 277(20):17649-17656. doi: 10.1074/jbc.M111704200 URL
[16]	Dobashi Y, Shoji M, Kitagawa M, et al. Simultaneous suppression of cdc2 and cdk2 activities induces neuronal differentiation of PC12 cells[J]. Journal of Biological Chemistry, 2000, 275(17):12572-12580. pmid: 10777547
[17]	Zhang YY, Zhang Y, Yao YB, et al. Butyrolactone-I from coral-derived fungus Aspergillus terreus attenuates neuro-inflammatory response via suppression of NF-κB pathway in BV-2 Cells[J]. Marine Drugs, 2018, 16(6):202. doi: 10.3390/md16060202 URL
[18]	Peng FC. Acetylcholinesterase inhibition by territrem B derivatives[J]. Journal of Natural Products, 1995, 58(6):857-862. pmid: 7673929
[19]	杨静明, 杨文聪, 刘亚月, 等. 化学诱导对一株海洋来源土曲霉C23-3次生代谢产物及其生物活性的影响[J]. 微生物学通报, 2019, 46(3):441-452.
	Yang JM, Yang WC, Liu YY, et al. Influence of chemical induction on the secondary metabolites and biological activities of a marine-derived fungal strain Aspergillus terreus C23-3[J]. Microbiology China, 2019, 46(3):441-452.
[20]	Guo CJ, Knox BP, Sanchez JF, et al. Application of an efficient gene targeting system linking secondary metabolites to their biosynthetic genes in Aspergillus terreus[J]. Organic Letters, 2013, 15(14):3562-3565. doi: 10.1021/ol401384v URL
[21]	Zhang LH, Feng BM, Zhao YQ, et al. Polyketide butenolide, diphenyl ether, and benzophenone derivatives from the fungus Aspergillus flavipes PJ03-11[J]. Bioorganic & Medicinal Chemistry Letters, 2016, 26(2):346-350. doi: 10.1016/j.bmcl.2015.12.009 URL
[22]	张翼, 鲍海燕, 聂影影, 等. 海洋真菌抗老年痴呆相关活性成分的筛选与追踪研究[J]. 现代食品科技, 2016, 32(11):63-71.
	Zhang Y, Bao HY, Nie YY, et al. Screening and tracing of anti-Alzheimer’s related bioactive constituents from marine fungi[J]. Modern Food Science and Technology, 2016, 32(11):63-71.
[23]	Papagianni M. Fungal morphology and metabolite production in submerged mycelial processes[J]. Biotechnology Advances, 2004, 22(3):189-259. pmid: 14665401
[24]	Schimmel TG, Coffman AD, Parsons SJ. Effect of butyrolactone I on the producing fungus, Aspergillus terreus[J]. Applied & Environmental Microbiology, 1998, 64(10):3707-3712.
[25]	Rutledge PJ, Challis GL. Discovery of microbial natural products by activation of silent biosynthetic gene clusters[J]. Nature Reviews Microbiology, 2015, 13(8):509-523. doi: 10.1038/nrmicro3496 pmid: 26119570
[26]	黄婷婷. 环酯肽抗生素吡啶霉素生物合成机制研究[D]. 上海:上海交通大学, 2011.
	Huang TT. Deciphering the mechanism of the pyridomycin biosynthesis[D]. Shanghai:Shanghai Jiao Tong University, 2011.
[27]	李亚伟, 赵林, 郝永伟, 等. 诱导纤维堆囊菌高产埃博霉素的种间微生物筛选及鉴定[J]. 生物技术通报, 2013, 10:137-141.
	Li YW, Zhao L, Hao YW, et al. Screening and identification of interspecies microorganisms inducing overproduction of epothiones in Sorangium cellulosum[J]. Biotechnology Bulletin, 2013, 10:137-141.

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

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[8]	杨小岚, 陈玉婵, 李浩华, 章卫民. 23株海洋真菌的分子鉴定及其抗植物病原真菌和细胞毒活性研究[J]. 生物技术通报, 2014, 0(8): 132-137.
[9]	李浩华陈玉婵王磊章卫民. 海洋真菌梅花状青霉FS83 抗菌抗肿瘤活性研究[J]. 生物技术通报, 2013, 0(1): 151-155.
[10]	. 抗生素和干扰素[J]. , 1996, 0(05): 64-66.
[11]	E.R.Ward. 植物转基因表达的化学调控[J]. , 1994, 0(01): 1-4.
[12]	李思经;. 转基因植物中基因表达的化学调节[J]. , 1993, 0(01): 18-19.