海洋植物源真菌代谢产物多样性与抗植物病原菌活性研究

The data from FAO revealed that more than 20% loss of crops are caused from plant-pathogens and insecticides, with most of them due to plant pathogens. It is therefore very urgent to discover and develop new, effective, and safe inhibitory agents against plant-pathogens with broad spectrum. Microbes are one of the most prolific sources for the discovery of such agents. In recent years, the search for structurally new and biologically active anti-plant pathogenic agents from marine microbes received a considerable attention. We recently obained a variety of endophytic fungi from marine plants and the preliminary results from a bioassay evaluation indicated that four fungal strains, namely, MA-21, EN-189, EN-201, and EN-220, displayed significant activity against various plant pathogens such as Valsa mali, Coniella diplodiella, and Fusarium oxysporium. The pre-chemical examination of these fungal strains revealed the presence of indolediterpenoids and indolediketopiperazine alkaloids in their culture extracts. Based on the above results in hand, the present project will focus on the study of secondary metabolites from the above four endophytic fungi. Using epigenetic manipulation such as putting environmental stress factors for the cultivation of the selected fungal stains, a series of structurally new metabolites with diverse structure and potent activity against plant-pathogens will be obtained. The stucture-activity relationship of these metabolites will be analyzed. The results from this project are hopefully to provide usefull information for the utilization of endophytes from marine plant resources.

据联合国粮农组织(FAO)统计，世界上每年因病虫害造成的粮食损失约占20%以上，其中植物病害占相当大的比重。发现新的、高效、安全、广谱的植物病害抑制剂已成为当务之急。微生物是发现新的植物病害抑制剂的重要来源。近年来，从海洋生物尤其是海洋微生物中发现结构新颖、活性显著的植物病害抑制剂受到了广泛重视。我们在前期研究中获得一系列海洋植物源内生真菌,经小规模培养发酵和活性筛选，发现菌株MA-21、EN-189、EN-201和EN-220的代谢产物对若干植物病原菌如苹果腐烂菌、葡萄白腐菌和棉花枯萎菌等具有显著的抑制活性，初步的代谢产物研究表明其主要活性成分是吲哚二萜、吲哚二酮哌嗪生物碱等。本项目拟在前期研究基础上，系统研究上述四株海洋植物源内生真菌的代谢产物，通过表观遗传修饰，诱导其产生结构新颖、活性显著的植物病原菌抑制剂，探讨代谢产物的分子多样性与构效关系，为海洋植物源内生真菌的应用提供科学依据。

海洋生物内生真菌代谢产物研究是目前海洋天然产物的研究热点之一。本项目按计划开展了海洋植物（红树林、海藻）源真菌代谢产物的化学多样性与抗植物病原菌活性研究，采用优化培养的策略，开展了不同真菌在多种培养条件的优化研究，并在优化的条件下进行了一定规模的发酵和代谢产物分离纯化与结构鉴定，从红树林来源的真菌Aspergillus tamarri MA-21、Rhizomucor variabilis EN-189、Penicillium oxalicum EN-201和海藻来源的真菌Eurotium cristatum EN-220中共分离获得139个单体化合物，采用现代波谱技术鉴定了所有化合物的分子结构，其中33个为国际上首次报道的新结构化合物，结构类型丰富多样，包括缩酚酸肽类、吲哚二萜类、混源萜类、二酮哌嗪类等。另外还从红树林真菌Penicillium bilaiae, P. brocae和Aspergillus nidulans的培养产物中发现了10个新结构化合物，包括2个含有三元环新骨架结构的倍半萜类化合物。对所有分离获得的单体化合物进行了抗农业病害菌、人类致病菌活性和抗氧化活性评价，发现若干化合物具有显著的活性，有进一步研究开发的潜力。