两株深海真菌中活性次生代谢产物的研究

Marine fungi are important sources for structurally unique and bioactive marine natural products，because of their biodiversities in taxonomy and ecology. Deep sea fungi have special metabolite systems after long term evolution, indicating the ability in producing lots of new compounds compared to their shallow-water counterparts. In previous study, we isolated more than 100 deep sea fungal strains and two of them showed significant antifouling and cytotoxicity activities. Based on that, we plan to systematically investigate the secondary metabolites and their bioactivities of the two deep sea fungal strains,which were isolated from sediments of the Indian Ocean about the depth of 4000 m. The techniques and methods of natural products chemistry, microbiology,marine chemical ecology and pharmacology will be applied. In this project, we will use kinds of fermentation and separation methods especially HPLC to isolate the secondary metabolites, and the structures of the isolates will be determined on the basis of spectroscopic data. All the compounds will be assayed according to pharmacology modals(such as cytotoxicities and antioxidant) and marine ecology modals (such as antifouling and anti-pathogenic bacteria activities). The SAR (Structure Activity Relationship) will also be discussed after the modification and optimization of the structures of bioactive metabolites.As a result, we wish that 1 or 2 lead compound(s) will be found, and make our great effort to the Research and Development of marine drugs and marine antifouling reagents.

海洋真菌的物种和生态多样性导致其次生代谢产物结构与活性的多样性，是活性天然产物的重要来源。深海真菌长期处在极端环境下，进化出独特的代谢系统，具有生成新奇结构活性化合物的潜力。课题组在 "中科院印度洋开放航次"采集的深海底泥中，分离出100余株深海真菌，发现其中两株具有显著的抗海洋生物污损和抗肿瘤活性，且代谢产物丰富。本项目拟在此基础上，综合运用天然药物化学、微生物学、海洋化学生态学和药理学等学科专业技术，对2株来源于印度洋4000米左右沉积物中的真菌活性次生代谢产物进行系统研究。通过多种方法优化发酵条件进行发酵，应用现代高效液相快速分离技术和各种波谱、光谱学手段，对其中的活性和微量成分分离和鉴定，并对所得的化合物进行海洋生态学（抗海洋病原菌和抗海洋生物污损）和药理学（抗肿瘤和抗氧化）双重活性评价，通过化学衍生、转化等手段进行构效关系探讨，发现一批活性化合物，为开发海洋防污剂和海洋药物基础。

海洋真菌的物种和生态多样性导致其次生代谢产物结构与活性的多样性，是活性天然产物的重要来源。深海真菌长期处在极端环境下，进化出独特的代谢系统，具有生成新奇结构活性化合物的潜力。本项目对对2 株来源于印度洋4000 米左右沉积物中分离的真菌中次生代谢产物进行系统研究。主要采用的活性模型为“藤壶幼虫附着实验”来模拟反映化合物对污损生物的作用和影响。本项目拟在此基础上，综合运用天然药物化学、微生物学、海洋化学生态学和药理学等学科专业技术，对4株来源于印度洋4000 米左右沉积物中的真菌活性次生代谢产物进行系统研究。通过多种方法优化发酵条件进行发酵，应用现代高效液相快速分离技术和各种波谱、光谱学手段，分离鉴定了40多个化合物，其中新化合物5个，发现了一批具有显著抗污损活性的吲哚生物碱类化合物。其中化合物A活性最好，我们对它进行了深入的作用机理和野外挂板实验研究.为开发海洋防污剂和海洋药物基础。