海洋弯孢霉菌丝形态对抗厌氧菌化合物Curvulamine发酵过程的调控及机制研究

海洋微生物次级代谢产物是新药源分子的重要来源。海洋弯孢霉IFB-Z10的重要次级代谢产物吲哚里西啶生物碱Curulamine（CA）具有类似于临床一线抗厌氧菌药物替硝唑的抑菌活性，是一种潜在的抗厌氧菌候选化合物。本课题组前期研究发现，CA的生物合成同海洋弯孢霉的菌丝形态密切相关，且发现钙离子的添加能调控菌丝形态，进而促进CA的合成，但相关分子机制尚不清楚。因此，本课题组拟采用冷冻切片、GFP2荧光标记等菌丝形态分析技术，从表观菌丝形态层面阐明钙离子添加对海洋弯孢霉菌丝形态的影响；运用代谢流分析及转录表达分析技术，从内在代谢调控层面阐明钙离子添加对CA生物合成的影响；利用双分子荧光互补及基因操作技术，研究钙离子添加调控海洋弯孢霉菌丝形态，进而促进CA生物合成的分子机制，将为调控海洋弯孢霉产CA及其他海洋真菌重要次级代谢产物的合成调控提供重要理论依据。

Marine-derived microorganisms are important sources of innovate pharmaceutical molecules. Curlamine (CA), a potential candidate compound for anti-anaerobic agents from marine-derived Curvularia sp. IFB-Z10, with an equal anti-anaerobic activity as that of tinidazole, one of the crucial clinical drugs. Previous research indicated an intimate-association between biosynthesis of CA and fungal morphology. Moreover, the addition of Ca2+ could significantly control the morphology, thus enhance the biosynthesis of CA. However, the relevant molecular mechanism has yet not been studied. Therefore, this project intends to illuminate the effect of Ca2+ on Curvularia sp. IFB-Z10 morphology via related techniques as freezing microtomy, GFP2 fluorescence labeling. Then, such technologies as metabolic flux analysis and transcriptional expression analysis would be utilized to clarify the internal relationship of Ca2+ addition and CA biosynthesis. Furthermore, the mechanism of stimulatory effects of Ca2+ on Curvularia sp. IFB-Z10 morphology and CA biosynthesis would be comprehensively investigated through the brand techniques of bimolecular fluorescence complementation and genetic manipulation. Such scientific conclusions would contribute not only to the biosynthesis of CA, but also provide vital theoretical basis to the study of synthesis of other crucial secondary metabolites derived from marine filamentous fungi.