Panepoxydone是由高等真菌野生革耳（Panus rudis）产生的一个NF-κB抑制剂，具有良好的抗肿瘤活性和潜在的药物开发前景，但是其生物合成机制不清楚。前期研究中我们发现饲喂L-苯丙氨酸可以明显增加panepoxydone类化合物的含量；饲喂叔丁基对苯二酚可以产生对应的panepoxydone的类似物。基于此，我们推测在P. rudis中很有可能首先由L-苯丙氨酸代谢形成对羟基苯甲酸，然后通过异戊烯基化、氧化脱羧、环氧化等反应形成panepoxydone。本项目拟通过同位素标记的前体饲喂实验阐明该化合物的生源途径，揭示高等真菌中苯丙氨酸到对羟基苯甲酸的代谢途径；并利用基因克隆、异源表达和体外酶催化功能验证的方法确定其生物合成中环氧化酶的功能。期望在基因和酶学水平上阐明其生物合成机制，揭示环氧环己烯酮类化合物产生的一般机制，为利用合成生物学生产和改造该类化合物奠定基础。

Panepoxydone is a NF-κB inhibitor produced by higher fungi Panus rudis, which has shown significant antitumor activity and clinical potential for the treatment of breast cancer. However, the biosynthetic pathway for panepoxydone is still not clear. In our previous study, we found the content of panepoxydone and its derivatives were obviously increased after feeding L-Phenylalanine. Besides, an analogues of panepoxydone was obtained after feeding tert-Butylhydroquinone. Based on these results, we proposed panepoxydone may be biosynthesized from L-Phenylalanine. In p. rudis, L-Phenylalanine may be degrade to form p-hydroxybenzoic acid, which is then followed by prenylation、oxidative decarboxylation and epoxidation. In this project, we will elucidate the biosynthetic pathway for panepoxydone by 13C-labeling studies, which will reveal the biosynthetic pathway for p-hydroxybenzoic acid from L-Phenylalanine in higher fungi, and try to identify the key epoxidase involved in its biosynthetic pathway by gene clone、heterologous expression and in vitro assay. These results will provide basic knowledge for understanding the biosynthetic pathway of epoxyquinone and generation of new derivatives with similar structure by synthetic biology.