海洋微生物的次级代谢产物是新药源分子的重要来源。海洋烟曲霉CY018的次级代谢产物烟曲霉文丙（Fumigaclavine C，FC）具有类似于环孢菌素A的抗炎免疫抑制活性，是一种潜在的免疫抑制剂候选化合物。本课题组前期研究发现，FC的生物合成同海洋烟曲霉的无性发育产孢密切相关，且渗透胁迫作用对二者均有显著影响，但相关分子机制尚待阐明。因此，本课题拟采用基因操作和色谱分析技术，从基因层面阐明海洋烟曲霉无性发育关键基因的表达对FC合成的影响；运用转录、表达分析技术，研究渗透胁迫对海洋烟曲霉无性发育及FC合成相关基因转录、表达的影响；利用双分子荧光互补及免疫共沉淀技术，研究渗透胁迫下发育全局调控蛋白Velvet与次级代谢全局调控蛋白LaeA的相互作用情况。阐明渗透胁迫调控海洋烟曲霉无性发育及FC合成的分子机制，将为调控海洋烟曲霉产FC及其它海洋真菌生产重要次级代谢产物的合成调控提供重要理论依据。

Marine environment is the important source of innovate pharmaceutical molecules. Fumigaclavine C (FC), a potential candidate compound for immunosuppressive agents from marine-derived Aspergillus fumigatus CY018, possesses the equal anti-inflammation activity as the clinic drug cyclosporin A. Based on our previous research, the biosynthesis of FC is intimately associated with conidiation, a stage of asexual development, and osmotic stress has significant impact on both procedures, however, the relavant molecular mechanism is yet not known. Therefore, this program aims to utilize the technologies of gene manipulation and liquid chromatographic-mass spectrometry technology (LC-MS) to clarify the impact of asexual development on FC biosynthesis firstly. Then through the technologies of transcription analysis and expression analysis, we could study the effects of osmotic stress on asexual development and FC biosynthesis of marine-derived Aspergillus fumigates CY018. Finally the protein-protein interaction of global developmental regulator Velvet and global secondary metabolic regulator LaeA under osmotic stress would be studied based on the methods of bimolecular fluorescence complementation and co-immunoprecipitation assay. The clarification of the molecular mechanism of osmolality-regulated asexual development and FC biosynthesis would contribute to the production of FC and provide a solid theoretical basis to the study of synthesis regulation of important secondary metabolites from other marine-derived filamentous fungi.