中文摘要
植物内生真菌无花果拟盘多毛孢能够产生多种结构新颖、活性广泛的次级代谢产物。其中chloropupkeananin是首次发现的含氯的三环癸烷类新骨架化合物,具有良好的抗菌、抗肿瘤及抑制HIV复制活性。前期工作表明该化合物可能来源于pestheic acid(PA)和iso-A82775C的Diels-Alder加成反应,但具体的合成途径和调控机制还一无所知。在成功克隆了上述两个化合物的生物合成基因簇后,我们初步阐明了PA的生物合成途径。在此基础上,本课题拟通过分子生物学手段解析iso-A82775C的生物合成途径,进而阐明chloropupkeananin的生物合成机制,同时开展PA和iso-A82775C生物合成的调控机制研究。本课题的研究将揭示chloropupkeananin形成过程中新的合成机制和新的调控机制,对该类化合物的理性改造和应用起到积极的推动作用。
英文摘要
Endophytic fungi have been demonstrated to be a rich source of biologically active metabolites with diverse structural features. Chemical investigations of the plant endophyte Pestalotiopsis fici led to the discovery of an array of novel metabolites including chloropupukeananin, the first chloropupukeanane derivative with a highly functionalized tricyclo-[4.3.1.03,7]-decane skeleton and related compounds showing significant antimicrobial, antitumor, and anti-HIV activities. Chloropupukeananin could be derived from the Diels-Alder adduct of pestheic acid and iso-A82775C based on the chemical studies. However, nothing is known about the biosynthesis of chloropupukeanane and its regulatory mechanism. Recently, we have identified the gene clusters for pestheic acid and iso-A82775C biosynthesis in P. fici, and elucidated the pestheic acid biosynthetic pathway. In this project, we will investigate the novel biosynthetic pathway of iso-A82775C, chloropupkeananin formation and the regulatory mechanism of pestheic acid and iso-A82775C biosynthesis.
