三株越前水母共附生真菌的抗菌活性物质研究

Today, the excessive use of antibiotics compounded by the paucity of new agents on the market has meant the problem of antibiotic resistance is fast escalating into a global health crisis. Therefore, efforts are urgently needed to develop and market new antibiotics with novel structure and mechanism. Marine microorganisms are an important source of antibacterial secondary metabolites, and the interest in marine microorganisms continues to grow every year, with fungi being a consistent source of active metabolites. Endozoic microorganisms inhabit the inner tissues of animals as specific microbial biota, and ecological interactions have evolved not only between the host and their endozoic microorganisms but also between the endozoic microorganisms such as bacteria and fungi, either in a symbiotic or competitive manner. Unlike free-living marine microorganisms, they biosynthesize unique secondary metabolites in a special ecological niche and often have interesting pharmacological properties. Of all ocean species, jellyfish are among the least studied by scientists, in part because of their lack of obvious utility to humans, and in part because of the specific challenges of working with them. All jellyfish sting their prey using nematocysts, also called cnidocysts, stinging structures located in specialized cells called cnidocytes, which are characteristic of all Cnidaria. Contact with a jellyfish tentacle can trigger millions of nematocysts to pierce the skin and inject venom, yet the sting of only some jellyfish species causes an adverse reaction in humans. So, the tentacles of a jellyfish are an important chemical defense mechanism, which meaning that it is possible to isolate some unique bioactive compounds from jellyfish Nemopilema nomurai derived microorganism. Our aim was to identify antibacterial metabolites from jellyfish-derived microorganisms. Twelve fungi and twelve bacterias were separeted from jelyfish Nemopilema nomurai. Guided by antibacterial activity against a panel of huaman and marine pathogens, we will investigate the chemical components of three fungal strains derived from the giant jellyfish Nemopilema nomurai. The structure and the biological evaluation of isolated compounds will be done. In addition, it is also interesting to analyze the structure-activity relationship for providing theoretical basis to further research in a productive manner.

随着抗生素的广泛使用和滥用，微生物的耐药性逐渐增强。与此同时，环境污染的加剧，社会和人文的变迁，新的致病菌和条件致病菌不断出现，这已经成为严重的社会问题。解决问题的最有效办法就是加大力度来开发新的抗生素。目前，从微生物中筛选具有抗菌活性的化合物正备受关注。由于海洋特殊的生态环境，海洋微生物中共附生微生物具有独特的特点，已逐渐成为研究焦点。鉴于共附生微生物与其寄主之间以及彼此之间复杂的相互关系，同时受水母本身化学防御机制影响，水母的共附生微生物可以产生一些结构新颖的具有抗菌活性的物质。使用现代色谱光谱等技术，本项目拟从三株越前水母的共附生真菌中提取分离及鉴定一系列结构独特的化合物，并进行抗菌活性研究。探讨同类化合物可能的生物合成途径和活性较好的化合物构效关系，对活性化合物进行结构优化和/或修饰，以寻找有更高抗菌生物活性的先导化合物，为新的抗生素的研究开发及临床上解决耐药菌问题奠定基础。

随着抗生素的广泛使用和滥用，微生物的耐药性逐渐增强。与此同时，环境污染的加剧，社会和人文的变迁，新的致病菌和条件致病菌不断出现，这已经成为严重的社会问题。解决问题的最有效办法就是加大力度来开发新的抗生素。鉴于共附生微生物与其寄主之间以及彼此之间复杂的相互关系，同时受水母本身化学防御机制影响，水母的共附生微生物可以产生一些结构新颖的具有抗菌活性的物质。鉴于共附生微生物与其寄主之间以及彼此之间复杂的相互关系，同时受水母本身化学防御机制影响，水母的共附生微生物可以产生一些结构新颖的具有抗菌活性的物质。为妥善解决水母大爆发带来的负面影响，本项目从水母共附生微生物的活性物质方面进行研究，同时也为深入发掘水母的利用价值提供了一个新的思路。本项目对三株越前水母Nemopilema nomurai共附生真菌进行化学成分研究，从中发现若干结构独特、新颖的化合物，并进行了一系列生物活性研究。共分离得到82个化合物，其中，水母共附生真菌的菌株Aspergillus fumigatus strain UWFP 503以及Aspergillus sp. PSBORB-4为同属不同种化合物，均产生大量的喹唑啉生物碱类化合物，说明这两种真菌菌株中存在相同或者类似的生物酶进行新陈代谢。新化合物fumigatoside B—D是首次分离得到的含有糖苷的喹唑啉生物碱，为研究喹唑啉生物碱类化合物的生物合成提供一个证据和支持。通过三种真菌分离提取的化合物结构比较，总结并分析越前水母共附生微生物天然产物的结构特点和生物合成途径，这为开发临床抗菌药物提供依据，具有很好的研究前景和理论价值。