放线菌YIM100497次生代谢产物研究
摘要
生物碱(alkaloid)是一类具有含氮的碱性有机化合物,大多数生物碱都具有复杂的环状结构,而且氮元素大多在其环内。生物碱来源广泛,是植物次生代谢产物中研究较多的一大类。同时,微生物次生代谢产物、海洋生物代谢产物研究中也有很多生物碱成分的报道。近年来,对从植物中分离出来的许多活性内生菌的研究日益增多,并从这些内生菌的发酵液中发现不少活性优良的次生代谢产物。
生物碱因其具有多种生物活性,被众多研究领域所关注,一直以来都是科学工作者们不断寻求新药、活性优良药的研究方向。临床中,生物碱可用来作为抗癌药、抗疟疾药、止痛药等药用制剂,同时还可以用来治疗帕金森综合症、高血压、中枢神经系统紊乱等疾病。本文第一章的主要内容是在基于查阅文献的基础上,对1950年至今从微生物次生代谢产物中分离出来的生物碱进行了总结归纳。
放线菌(Actinomycete)YIM100497采自云南野生动物园白羊驼动物粪便,对其形态、生理生化特性、细胞壁化学组分以及16SrRNA序列进行研究分析,鉴定该菌株属于链霉菌属(Streptomyces sp.)。本文第二章报道了放线菌YIM100497和95株真菌发酵产物的化学和生物活性筛选。通过对放线菌YIM100497在8种不同发酵培养基和95株真菌在2种发酵培养基上的代谢产物进行TLC检测分析及生物活性实验结果分析,确定了38#培养基作为放线菌YIM100497的种子培养基,2#培养基为放线菌YIM100497的发酵培养基；PDB培养基为真菌的种子培养基和发酵培养基。
在化学筛选的基础上,本文第三章主要对放线菌YIM10049发酵液的化学成分进行分离分析研究。运用硅胶柱层析、凝胶柱层析、半制备HPLC等方法进行分离纯化,以IR、ESI-MS、NMR等波谱技术进行结构鉴定,从其发酵液中共分离并鉴定了14个化合物,还有1个化合物尚未鉴定。这14个化合物结构分别为：N-((S)-1-phenylethyl)-2-hydroxyl-acrylimine (1)、(S)-N-nitroso-l-amino-p-hydroxy phenylethanol (2)、β-咔啉(3)、吲哚-3-羧酸(4)、胸腺嘧啶脱氧核苷(5)、环(L-丙氨酸-L-酪氨酸)(6)、邻苯二甲酸辛二酯(DEHP)(7)、腺嘌呤核苷(8)、海藻糖(9)、蔗糖(10)、β-谷甾醇(11)、胡萝卜苷(12)、大豆皂苷I(soyasaponin I)(13)和4',7二羟基-异黄酮(14),其中化合物1和2为2个结构新颖的生物碱。
Alkaloids are a group of complex nitrogens-containing compounds which are derived from the microorganism, the marine organism and plants. In recent years, there has a drastic increase in discovering endophytes that produce novel metabolites with biological activities.Much effort has been made to discover new biological alkaloids for the treatment of a wide range of diseases, for example used as anticancer agents, analgesics, and antimalarials, and in the treatment of parkinsonism, hypertension and centeral nervous system disorders. The first chapter of this paper introduces the research of the alkaloids based on the literatures,
The actinomycetal strain, designated YIM100497was isolated from Lanma pacos in Yunnan Wild Animals Park, and identified as Streptomyces sp. by analysing of morphological characteristics, physiological and biochemistry characteristics, chemical constituent of cell wall and16SrRNA gene sequences.The second chapter of the paper reports the chemical screening about the actinomyces YIM100497and95fungi, and then their activities are discussed. By evaluating the metabolites from the actinomyces YIM100497and the fungi in different culture broths on the TLC,38#culture broth was selected as the seed culture broth,2#culture broth was the fermentation broth for strain YIM100497, and PDB culture broth was selected as the the seed culture broth and the fermentation broth for the fungi.
On the base of the chemical screening, the study on the secondary metabolism from the fermentation broth of actinomycete YIM100497is carried out in the third chapter of this paper. From the fermentation broth, two new compounds, twelve known compounds and an unidentified compound were isolated by silica chromatograhy, gel chromatography and semi-preparative HPLC, and their structures were identified as N-((S)-1-phenylethyl)-2-hydroxyl-acrylimine (1),(S)-N-nitroso-1-amino-p-hydroxy phenylethanol (2), β-carbolin (3), indole-3-carboxylic acid (4),2'-deoxythymidine (5), Cyclo(L-Ala-L-Tyr)(6), bis(2-ethylhexyl) phthalate (7)(DEHP), adenosine (8), trehalose (9), sucrose (10), β-sitosterol (11), β-daucosterol (12), soyasaponin I (13), 4',7-dihydrox-yisoflavone (14), by analysing the spectroscopic data of IR, HRESIMS, NMR.
生物碱因其具有多种生物活性,被众多研究领域所关注,一直以来都是科学工作者们不断寻求新药、活性优良药的研究方向。临床中,生物碱可用来作为抗癌药、抗疟疾药、止痛药等药用制剂,同时还可以用来治疗帕金森综合症、高血压、中枢神经系统紊乱等疾病。本文第一章的主要内容是在基于查阅文献的基础上,对1950年至今从微生物次生代谢产物中分离出来的生物碱进行了总结归纳。
放线菌(Actinomycete)YIM100497采自云南野生动物园白羊驼动物粪便,对其形态、生理生化特性、细胞壁化学组分以及16SrRNA序列进行研究分析,鉴定该菌株属于链霉菌属(Streptomyces sp.)。本文第二章报道了放线菌YIM100497和95株真菌发酵产物的化学和生物活性筛选。通过对放线菌YIM100497在8种不同发酵培养基和95株真菌在2种发酵培养基上的代谢产物进行TLC检测分析及生物活性实验结果分析,确定了38#培养基作为放线菌YIM100497的种子培养基,2#培养基为放线菌YIM100497的发酵培养基；PDB培养基为真菌的种子培养基和发酵培养基。
在化学筛选的基础上,本文第三章主要对放线菌YIM10049发酵液的化学成分进行分离分析研究。运用硅胶柱层析、凝胶柱层析、半制备HPLC等方法进行分离纯化,以IR、ESI-MS、NMR等波谱技术进行结构鉴定,从其发酵液中共分离并鉴定了14个化合物,还有1个化合物尚未鉴定。这14个化合物结构分别为：N-((S)-1-phenylethyl)-2-hydroxyl-acrylimine (1)、(S)-N-nitroso-l-amino-p-hydroxy phenylethanol (2)、β-咔啉(3)、吲哚-3-羧酸(4)、胸腺嘧啶脱氧核苷(5)、环(L-丙氨酸-L-酪氨酸)(6)、邻苯二甲酸辛二酯(DEHP)(7)、腺嘌呤核苷(8)、海藻糖(9)、蔗糖(10)、β-谷甾醇(11)、胡萝卜苷(12)、大豆皂苷I(soyasaponin I)(13)和4',7二羟基-异黄酮(14),其中化合物1和2为2个结构新颖的生物碱。
Alkaloids are a group of complex nitrogens-containing compounds which are derived from the microorganism, the marine organism and plants. In recent years, there has a drastic increase in discovering endophytes that produce novel metabolites with biological activities.Much effort has been made to discover new biological alkaloids for the treatment of a wide range of diseases, for example used as anticancer agents, analgesics, and antimalarials, and in the treatment of parkinsonism, hypertension and centeral nervous system disorders. The first chapter of this paper introduces the research of the alkaloids based on the literatures,
The actinomycetal strain, designated YIM100497was isolated from Lanma pacos in Yunnan Wild Animals Park, and identified as Streptomyces sp. by analysing of morphological characteristics, physiological and biochemistry characteristics, chemical constituent of cell wall and16SrRNA gene sequences.The second chapter of the paper reports the chemical screening about the actinomyces YIM100497and95fungi, and then their activities are discussed. By evaluating the metabolites from the actinomyces YIM100497and the fungi in different culture broths on the TLC,38#culture broth was selected as the seed culture broth,2#culture broth was the fermentation broth for strain YIM100497, and PDB culture broth was selected as the the seed culture broth and the fermentation broth for the fungi.
On the base of the chemical screening, the study on the secondary metabolism from the fermentation broth of actinomycete YIM100497is carried out in the third chapter of this paper. From the fermentation broth, two new compounds, twelve known compounds and an unidentified compound were isolated by silica chromatograhy, gel chromatography and semi-preparative HPLC, and their structures were identified as N-((S)-1-phenylethyl)-2-hydroxyl-acrylimine (1),(S)-N-nitroso-1-amino-p-hydroxy phenylethanol (2), β-carbolin (3), indole-3-carboxylic acid (4),2'-deoxythymidine (5), Cyclo(L-Ala-L-Tyr)(6), bis(2-ethylhexyl) phthalate (7)(DEHP), adenosine (8), trehalose (9), sucrose (10), β-sitosterol (11), β-daucosterol (12), soyasaponin I (13), 4',7-dihydrox-yisoflavone (14), by analysing the spectroscopic data of IR, HRESIMS, NMR.
引文
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