海洋藻栖木霉次生代谢产物及化学防御功能研究

Surviving in the ocean, marine macroalgae are faced with various ecological stresses, including the competition of microalgae for nutrients and space, pathogenic microbes, and herbivorous animals. Algicolous fungi contribute to the survival of marine macroalgae by producing some defending metabolites. Trichoderma spp. are known for their biocontrol functions, and the antagonistic potential of their secondary metabolites is one of the key mechanisms. Especially, a large amount of metabolites remain unknown by analysis of Trichoderma genomes. Combined with the novelty of secondary metabolites from marine/algicolous Trichoderma spp. and little consideration for their ecological functions, marine macroalga-derived Trichoderma strains will be taken as the objects of this project. The effects of marine environmental factors and chemical epigenetic modification on their secondary metabolisms will be explored. Based on the OSMAC (One Strain-Many Compounds) strategy, the structural diversity of secondary metabolites, along with their differences from the metabolites of other origin, will be analyzed. Additionally, their inhibition of marine microalgae and pathogenic microbes and toxicity to marine animals will be evaluated. The purpose is to disclose the ability of algicolous Trichoderma spp. to maintain the “ecological niche” of marine macroalgae from the chemical defense perspective, especially their antagonism against red-tide microalgae and alga-pathogenic microbes. This project may result in the isolation and identification of 200 secondary metabolites, including ca. 30 new compounds, 2-4 new skeletons, and 1-3 highly active molecules, publication of 7-10 SCI papers, and application of 1-3 patents.

大型海藻在海洋中生存面临着多方面的生态压力，包括微藻竞争、微生物病害、动物饲食等，作为可能的抵御机制之一，藻栖真菌表现出一定的化学防御潜力。鉴于木霉显著的生防功能、次生代谢产物的抗生作用和生产潜力，以及海洋和海藻来源木霉次生代谢产物的新颖性与生态功能研究的缺乏，本项目计划选取大型海藻来源的木霉菌株为对象。研究海洋环境因素和化学表观遗传修饰等对藻栖木霉次生代谢的影响，并基于“单菌多产物”(OSMAC)策略，研究产物的结构多样性，与其它来源木霉的产物差异性，以及海洋微藻抑制活性、海藻病原菌抑制活性和海洋动物毒性。旨在从化学防御的角度揭示藻栖木霉次生代谢产物在宿主大型海藻“生态位”维持中的作用，特别是对赤潮灾害和海藻病害的防治意义。项目预期分离鉴定次生代谢产物200个左右，其中新化合物约30个、新骨架类型2-4个、具有应用前景的活性分子1-3个，发表SCI论文7-10篇，申请发明专利1-3项。

大型藻类植物在海洋中生存面临着微藻竞争、微生物病害、动物饲食等多方面的生态压力。为了探索藻栖木霉的化学防御潜力，本项目通过藻栖木霉菌种库的构建与活性菌株筛选、次生代谢产物的结构特性与多样性研究、次生代谢产物的化学防御功能评价，建立了300余株规模的藻栖木霉菌种库，完成了其中9株菌次生代谢产物的研究，分离鉴定次生代谢产物200个左右，其中新化合物74个，结构类型涵盖单萜、倍半萜、二萜、甾体、聚酮、生物碱、肽类，其中5个(3类)为新骨架化合物，4个萜类结构入选热点化合物，还有一些罕见骨架或取代类型的分子。筛选发现活性新化合物64个，其中具有海洋微藻抑制活性的56个，细菌抑制活性的26个，动物毒性作用的13个，特别是其中10个具有显著的赤潮微藻抑制作用，在海洋赤潮灾害防治方面具有一定的应用前景。目前已发表研究论文15篇，其中SCI论文14篇；申请发明专利16项，其中已获授权6项。项目发现的新化合物占藻栖木霉新化合物总量的90%以上，占木霉新化合物总量的10%左右，丰富了藻栖木霉次生代谢产物的结构多样性，深化了对藻栖木霉次生代谢产物结构特性与生态防御功能的认识，为藻栖木霉资源的开发利用奠定了科学基础。