无花果拟盘多毛孢菌独特化合物的深入研究

Chemical studies of the endophytic fungus Pestalotiopsis fici, isolated from the branches of Camellia sinensis, have led to the discovery of 30 compounds, 24 of which were new metabolites including nine intermediates or congeners of unique compounds. These metabolites were evaluated against multiple targets and some of them displayed significant cytotoxicity against a small panel of human tumor cell lines. The discovery of the nine unique compounds further improved their biosynthetic pathways based on Diels-Alder reaction. However, there are other possible biosynthetic intermediates or terminal products of these unique compounds in accordance with Diels-Alder reaction mechanism. In addition, the formation mechnism of these complex natural products, as well as the stereoselectivity difference of their precursors in vitro and in vivo needs to be further clarified. On the basis of above considerations, the objective compounds will be found by deep chemical investigation of P. fici. In addition, the biomimetic synthesis and biosynthetic pathways of these novel secondary metabolites will be studied. The results of this project will proof and perfect the biosynthetic pathways of these unique compunds by identifying biosynthetic intermediates, and reveal the existence of naturally diversified Diels-Alder reaction cascades in the fungus.

在青年科学基金项目的支持下，从茶内生无花果拟盘多毛孢菌（Pestalotiopsis fici）中获得了30个化合物，其中24个为新化合物，包括9个结构独特化合物的中间体及类似物；活性评价结果表明部分新化合物具有显著的细胞毒活性；这些复杂天然产物的发现进一步完善了前期研究中提出的基于Diels-Alder反应的生物合成途径。然而根据Diels-Alder反应机理，推测仍有其它中间体或终产物存在的可能。另外，这些结构独特天然产物的形成机制，以及它们前体化合物体内外反应立体选择性差异还有待于深入研究。基于如上考虑，本研究将继续深入挖掘该菌中结构独特的化合物，并对其进行仿生合成研究，同时开展前体化合物和终产物的生物合成研究。实施本研究不仅获得新结构活性化合物，为药物先导化合物提供备选分子，揭示Diels-Alder加成串联反应在真菌中的多样性，同时完善并验证该类化合物的生物合成途径。

项目执行期间，从真菌菌中获得了结构独特的次级代谢产物，已获得33个化合物，包括16个新化合物，其中7个化合物有肿瘤细胞毒活性，1个化合物具有抗真菌活性。此外，对两个真菌天然产物iso-A82775C和pestheic acid的生物合成途径进行了初步研究，确定了部分酶的功能。目前，已发表SCI论文8篇。