螳螂肠道真菌（Daldinia eschscholzii IFB-TL01）和海鱼肠道真菌（Curvularia sp. IFB-Z10和Chaetomium globosum 1C51）不仅产生小分子酚和/或胺，而且通过酚-酚、酚-胺和胺-胺之间的多方式缩合将其组装成一系列骨架全新的活性聚酮和生物碱。本项目拟深入研究这些真菌酚和胺单元产生和耦合的生物合成过程及其调控策略、探讨酚和胺单元拼合成多种骨架新颖分子的化学机制；在此基础上优化发酵条件、分离富集新骨架产物、结合活性评价优化发现新先导化合物。该工作预计能构建微生物聚酮和生物碱骨架的新颖化与多样化的方法与策略，或为之奠定重要基础；有关其生物合成途径研究有望挖掘出新的基因簇和新反应（现象）；结合生物活性研究有望发现骨架全新的先导化合物，为抗菌、抗炎、抗老年痴呆和抗痛风新药创制提供新起始分子。

Mantis- (Daldinia eschscholzii IFB-TL01) and marine fish-associated fungi (Curvularia sp. IFB-Z10 and Chaetomium globosum 1C51) are unique in synthesizing an array of bioactive polyketides and alkaloids with novel carbon skeletons from the phenolic and amine units. The assemblage primarily includes the promiscuous coupling of small molecule phenolic and amine units under the catalysis of fungal enzymes. But the detailed biosynthetic pathways need to be addressed. This project is intended to clarify the chemistry, biological mechanism, selectivity determinant(s) and skeletal diversifications. With such knowledge, the fermentation will be optimized aiming at higher yields of skeletally novel polyketides and alkaloids, which, after purification, will be evaluated for novel lead compounds highly desired for the development of new antibacterial, antiinflammatory, anti- Alzheimer's disease and anti-gout drugs.