深海真菌抗植物病原真菌菌株的筛选及其活性物质研究

Plant pathogenic fungi are the major groups of plant pathogens, they cause large loss in agriculture and forestry production every year. Currently, antibiotics used for controlling plant diseases originated from terrestrial actinomycetes. Searching for new microbial resources and antibiotics become more and more difficult since terrestrial microorganisms have been excavated and utilized for so long time. Moreover, some plant pathogenic fungi become resistant to current antibiotics and new pathogens are emerging. Therefore, continuous develpment of new efficient agricultural antibiotics are in urgent need. Deep sea derived fungi with special living environment and unique metabolic pathway are emerging strategic resources for seeking antifungal substances. Based on our previous work, the project will utilize deep sea derived fungi from the South China Sea to obtain strains with high antifungal activity using high throughput culturing and screening method. Comprehensive techniques including microbiology, natural product chemistry and pharmacology will be applied to the project. The secondary metabolites of these active strains will be isolated and purificated guided by antifungal activity against important plant pathogens and their structures will be elucidated by spectroscopic data analysis. The goal of this proposal is to obtain lead compounds with significant activity against plant pathogenic fungi from deep sea derived fungi, which will lay an important foundation for developing new efficient agricultural antibiotics with independent intellectual property rights in China in the future.

植物病原真菌是植物病害的主要病原微生物，每年给农林业生产带来巨大损失。目前应用于植物病害防治的农用抗生素来源于陆地放线菌，随着陆地微生物资源的不断发掘和利用，寻找新的微生物资源及其产生的新型抗生素已非常困难，而且病原菌对现有的抗生素产生耐药性，同时还产生新的病害。因此，迫切需要不断开发新型高效的农用抗生素。深海真菌因其生存环境特殊,代谢方式独特,是寻找抗菌活性物质的新兴战略资源。本项目拟在前期工作的基础上，以南海深海真菌为研究材料，通过高通量培养筛选技术获取高活性菌株，综合运用微生物学、天然产物化学和药理学专业技术，以抗植物重要病原真菌活性为指导，对活性菌株的代谢产物进行分离纯化和结构鉴定，获得抗植物病原真菌活性显著的先导化合物，为今后开发具有我国自主知识产权的新型、高效的农用抗生素奠定重要的物质基础。

植物病原真菌是植物病害的主要病原微生物。随着陆地微生物资源的不断发掘和利用，从中寻找防治植物病害的新型农用抗生素已非常困难，而且病原菌对现有的抗生素产生耐药性。深海真菌因其生存环境特殊，代谢方式独特，是寻找农用抗生素的新兴战略资源。因此对深海真菌活性代谢产物的开发利用，具有重要的科学意义和经济价值。本项目在前期研究基础上，对已分离到的深海真菌通过高通量筛选技术，获得了9株抗植物病原真菌活性的深海真菌。对这些目标菌株进行大量发酵培养得到粗提物，进而分离纯化得到单体化合物，并进行结构鉴定和活性测试，共分离鉴定了145个化合物，其中新结构化合物28个，新天然产物4个，经活性测试，发现抗植物病原真菌活性化合物11个，其中活性显著的化合物3个，分别是1,2,3,4-tetrahydro-2-methyl-3-methylene-1,4-dioxopyrazino [1,2-a]indole (FS110-10)、6-deoxy-5a,6-didehydrogliotoxin (FS140-11)、5a,6-didehydrogliotoxin (FS140-12)，它们对植物病原真菌的EC50值范围处于80-100 ug/mL之间。另外，通过其他活性测试，还发现具有较好抗肿瘤活性的化合物3个，具有显著的葡萄糖苷酶抑制活性的化合物1个。本项目为从海洋微生物中发掘抗植物病原真菌活性先导化合物，为开发具有我国自主知识产权的新型农用抗生素提供了重要的化学实体，同时，对于丰富微生物天然产物和发掘其他活性物质具有十分重要的意义和广阔的应用前景。