海藻是抗菌、抗赤潮、抗肿瘤等克生物质的主要生产者，含氮和卤代化合物是其克生物质的主要类型。近年来在近海海域爆发成"绿潮"的海藻浒苔具有抗赤潮活性，而共附生微生物可能是其克生物质的真正来源，申请者发现其共附生真菌的代谢产物具有抗菌和抗肿瘤活性。本项目拟在此基础上，以赤潮异湾藻、白色念珠菌、血管荧光标记斑马鱼及肿瘤细胞为活性模型，以TLC、LC-UV/MS为化学模型，分离筛选浒苔放线菌和真菌Talented菌株；利用表观遗传修饰，"唤醒"浒苔真菌中的"沉睡"基因，将一般浒苔真菌株转化为Talented菌株；通过拟生态培养和高盐胁迫，诱导浒苔微生物Talented菌株产生具有抗赤潮、抗菌和血管生成抑制作用的含氮、卤代等抗癌活性的克生物质。研究不仅为抗菌和抗癌自主创新药物的研究提供候选化合物及其产生菌，还将为"赤潮"和"绿潮"海洋灾害的防治与利用以及海洋藻类与其微生物之间的共生关系提供基础资料。

Algae are one of the major sources of allelopathic natural products with antimicrobial, anti-red tide, and anti-tumor activities. These active products mainly belong to nitrogen containing and halogenated compounds. Previous study revealed that the seaweed Enteromorpha prolifera blooming into green tide near the seacoast of Qingdao showed anti-red tide against Heterosigma akashiwo, Amphidinium hoefleri, Skeletonema costatum, Karenia mikimitoi and Alexandrium tamarense, indicating that there existed anti-red tide compounds in E. prolifera. And the real source of these allelochemicals might be algicolous microbes that need to be research. Our study also showed that the algicolous fungal metabolites of E. prolifera exhibited cytotoxicity against HL-60 and MCF-7 cell lines with angiogenesis inhibition and antimicrobial effects on Canidia albican, Staphylococcus aureus, Bacillus subtilis, Aerobacter aerogenes, Escherichia coli and Pseudomonas aeruginosa. Based on these findings, the project is planned to obtain antimicrobial, anti-red tide, and anti-tumor products with angiogenesis inhibition from the algicolous actinomyces and fungi associated with E. prolifera. By integrated use of chemical detections (TLC, LC-UV/MS) and bioassay against H. akashiwo, C. albican and MCF-7, as long as the angiogenesis inhibition in vascular fluorescent transgenic zebrafish embryos, the algicolous microbial talented strains will be isolated and identified. And the rest common strains will be converted into the talented strains in this project by means of epigenetic modifications that could be used to activate the silent genes to code fungal secondary metabolites. In addition, biomimetic culture and high salt stress will be applied to induce algicolous actinomyces and fungi to produce structurally new and diverse allelopathic natural products containing nitrogen and halogen atoms. The project, after the implementation, will be predicted to not only provide new candidate compounds for discovery of anti-bacterial and anti-cancer drugs with independent intellectual property rights, but also provide basic data for the prevention of the marine disasters, red tide and green tide, as well as the exploration of the symbiotic relationship between marine algae and their microbes.