豨莶草内生真菌 Alternaria brassicicola 中新颖的壳梭菌素类化合物及其生物合成研究

Fusicoccanes (FCNs) is a class of terpenoids with novel 5-8-5 tricyclic scaffold and exhibit significant bioactivities, which have attracted much attention from natural medicine researchers. Our previous chemically investigation led to 15 novel FCNs (including 3 new scaffolds) from the endophytic fungi Alternaria brassicicola of Siegesbeckia puescens. In vitro activity test showed the isolated FCNs could significantly inhibit growth of eukemia cells. . In this project, a series of FCNs will be mined from A. brassicicola by culture condition optimization, silent genes activation, metabolic flow regulation, heterologous expression and functional gene knockout methods. The FCNs will be seperated and identified by modern chromatographic and spectral techniques, the related activity-structure relationships will be illuminated. Bioinformatics, molecular genetics and chemistry techniques will be used to investigate the functions of key genes, and to elucidate the biosynthetic pathway of FCNs. The implementation of the project can not only obtain more FCNs candidates for anti leukemia, but also provide a basis for the combinatory biosynthesis of these special terpenoids.

壳梭菌素（fusicoccanes,FCNs）是一类具有5-8-5三环骨架的二萜类化合物，其独特的结构和显著的生物活性引起了天然药物研究者的兴趣。项目前期从药用植物豨莶草(Siegesbeckia puescens)的内生真菌Alternaria brassicicola中发现了一系列新颖的FCNs(其中包括3类新骨架),活性测试显示这些FCNs能诱导白血病细胞凋亡和周期阻滞作用。. 本项目拟采用培养条件优化、沉默基因激活、代谢流调控、异源表达、功能基因敲除等生物学手段，进一步挖掘A. brassicicola中的FCNs并进行活性测试，以期发现新颖的抗白血病先导化合物；同时，以生物信息学分析为指导，克隆和鉴定A. brassicicola中的FCNs生物合成基因簇，以阐明其生物合成途径。项目的实施，既可为抗白血病药物提供更多的候选分子，又可为FCNs的组合生物合成打下基础。

壳梭菌素（fusicoccanes,FCNs）是一类具有 5-8-5 三环骨架的二萜类化合物，其独特的结构和显著的生物功能引起了天然药物研究者的兴趣。本项目采用培养条件优化、沉默基因激活、代谢流调控等生物学手段，对内生真菌Alternaria brassicicola xxc中的FCNs进行了深度挖掘，发现了60多个一系列新颖的FCNs(其中包括6类新骨架)；活性测试结果显示，部分FCNs具有良好的抗炎和抗白血病活性，具有进一步研究和开发的学术价值和应用价值；同时，以生物信息学分析为指导，克隆和鉴定A. brassicicola xxc中的FCNs生物合成基因簇，阐明其生物合成途径，为其组合生物合成打下了基础。