中文摘要
共生真菌Curvularia sp. IFB-Z10可以产生一系列具有显著抗口腔厌氧病原菌活性、骨架全新的生物碱。本项目通过基因敲除、表观遗传修饰等方式,揭示该菌株生物碱生物合成基因簇、关键基因及其功能;推导出其完整合理的生物合成途径;通过组合生物合成,采用基因调控、酶抑制等策略,诱导、构建新生物碱以及结构骨架全新的化合物,进而评价其生物活性,有望全面发掘骨架全新的具有显著抑制厌氧菌的药源分子。
英文摘要
The symbiotic fungus Curvularia sp. IFB-Z10 can produce a series of new alkaloids with completely new carbon skeletons and effective anti-oral anaerobic pathogenic activities. The project intends to reveal the biosynthetic gene clusters, key genes and their functions responsible to the alkaloid production in the fungus, via the approaches including gene deletion and epigenetic modification; then elucidate the complete and reasonable biosynthetic pathways of the secondary metabolites; and through combinatorial biosynthesis by strategies such as the gene regulation and the enzyme inhibition, induce the production of new alkaloids and compounds with novel carbon scaffolds, then evaluate their biological activity, to fully explore the new drug lead molecules with complete new carbon scaffolds and significant inhibition of the anaerobes.
