小叶香茶菜中两株内生真菌的次生代谢产物研究

	小叶香茶菜中两株内生真菌的次生代谢产物研究
	夏江南
导师	孙汉董,普诺·白玛丹增
关键词	香茶菜，内生真菌，对映-贝壳杉烷型二萜，细胞毒活性，次生代谢产物，地杯菌属 Isodon, ent-Kaurane, Endophytes, Cytotoxicity, Secondary Metabolites, Geopyxis, Neosetophoma
摘要	微生物次生代谢产物是先导化合物的重要来源，在现代新药研发中具有重要地位。植物内生真菌作为一类生境特殊的微生物，其次生代谢易受到宿主植物影响，进而能够产生结构丰富、活性优异的天然产物。有趣的是，植物内生菌与宿主植物长时间共同进化，其可获得产生宿主植物次生代谢产物的能力。为寻找具有可持续发展前景的新颖天然小分子，本论文对青藏高原地区的九种香茶菜植株中的内生真菌进行了系统筛选，并对从小叶香茶菜中发现的两株菌进行了次生代谢产物研究。本论文主要由两部分组成，第一部分详细阐述了内生菌株的鉴定与筛选。基于研究组前期的研究，本研究采用了包含文献调研、HPLC分析以及“LC-MS/MS-GNPS”分析的三级筛选策略，结合主要次生代谢产物分析，对九种香茶菜属植物中的内生真菌进行了系统的培养、鉴定与筛选，并成功获得了722株内生真菌，其分别来自33个属66个种。随后基于筛选结果，选取两株源自小叶香茶菜的“天才真菌”Geopyxis sp. XY93和Neosetophoma sp. XY91开展了深入的次生代谢产物研究；第二部分系统论述了两株真菌次生代谢产物的分离纯化、结构鉴定与生物活性测试工作。借助色谱层析、波谱分析和X-单晶衍射等手段，从上述两株内生真菌中共获得了32个化合物，其中新化合物18个，包括3个新颖骨架。首次从一株香茶菜属植物的内生菌中发现了系列宿主植物的特征化学成分——对映-贝壳杉烷型二萜、松香烷型二萜和海松烷型二萜。此外，从另一株内生真菌中获得了系列结构新颖具复杂环系结构的杂萜。生物活性测试显示部分含有不饱和酮片段的二萜对肝癌细胞具有显著抑制活性。本论文丰富了香茶菜属植物内生菌次生代谢产物的研究内容，同时完善了本研究组对内生菌株筛选的策略，并为后续探究香茶菜属植物内生菌与宿主植物的相互作用奠定了研究基础。; Microbial secondary metabolites, as an important source of lead compounds, play an important role in the development of new drugs. Some secondary metabolites, possessing novel structures and potent bioactivities, are able to be produced from plant endophytic fungi, a type of microorganisms with unique habitats, due to the regulation of secondary metabolite biosynthesis of endophyte are susceptible to its hosts. Intriguingly, the secondary metabolites, which are the same as or similar to those from the host plants, are likely to be generated from endophytic fungi, after a long-term co-evolution between plants and endophytes. In this thesis, the endophytic fungi from nine Isodon plants, collected from the Tibetan Plateau, were screened to discover novel natural molecules with sustainable prospect. Fortunately, two promising fungi were obtained and subjected to systematic research about their secondary metabolites. This dissertation was mainly composed by two parts. The first part elaborated the identification and selection of fungal strains. Based on the experience of our previous studies, we have adopted a tertiary screening strategy together with principal metabolites analysis, including literature analysis, HPLC profiling and "LC - MS/MS – GNPS analysis", to sift the strains from nine species of Isodon plant. Subsequently, 722 endophytic strains were successfully acquired, including 33 genera and 66 species. Furthermore, two "talent strains" (Geopyxis sp. xy93, Neosetophoma sp. xy91) were discovered. The second part systematically discussed the isolation, purification, structural identification and biological activity assay of the secondary metabolites from above two fungi. By column chromatography, spectral analysis and X-ray single crystal diffraction, 32 compounds were isolated and identified from the two endophytic fungi, including 15 new compounds (three new skeletons). For the first time, a series of characteristic chemical constituents of Isodon plants were found from the metabolites of an endophytic fungi, such as ent-kaurane, ent-pimarane, and ent-abietane diterpenoid. Besides, a series of meroterpenoids with complex macrocyclic structures were also obtained from the metabolites of the other strain. The results of subsequent bioactive assays showed that some compounds with unsaturated ketone motif displayed significant inhibitory activity against HCC cells. This paper enriched the content of secondary metabolites research of endophytes inhabiting Isodon genus, supplemented the screening strategies of endophytes, and provide the basis for further exploring the interaction between endophytes of Isodon plant and host plants in the future.
语种	中文
	2022-05
学位授予单位	中国科学院大学
文献类型	学位论文
条目标识符	http://ir.kib.ac.cn/handle/151853/75114
专题	昆明植物所硕博研究生毕业学位论文
推荐引用方式 GB/T 7714	夏江南. 小叶香茶菜中两株内生真菌的次生代谢产物研究[D]. 中国科学院大学,2022.

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