PDF(Pubmed)
Abstract：
Cantharidin is a toxic defensive substance secreted by most blister beetles when attacked. It has been used to treat many complex diseases since ancient times and has recently regained popularity as an anticancer agent. However, the detailed mechanism of the cantharidin biosynthesis has not been completely addressed. In this study, we cloned McSTE24 (encoding STE24 endopeptidase) from terpenoid backbone pathway, McCYP305a1 (encoding cytochrome P450, family 305) and McJHEH [encoding subfamily A, polypeptide 1 and juvenile hormone (JH) epoxide hydrolase] associated to JH synthesis/degradation in the blister beetle Mylabris cichorii (Linnaeus, 1758, Coleoptera: Meloidae). Expression pattern analyses across developmental stages in adult males revealed that the expressions of 3 transcripts were closely linked to cantharidin titer exclusively during the peak period of cantharidin synthesis (20-25 days old). In contrast, at other stages, these genes may primarily regulate different biological processes. When RNA interference with double-stranded RNA suppressed the expressions of the 3 genes individually, significant reductions in cantharidin production were observed in males and also in females following McJHEH knockdown, indicating that these 3 genes might primarily contribute to cantharidin biosynthesis in males, but not in females, while females could self-synthesis a small amount of cantharidin. These findings support the previously hypothesized sexual dimorphism in cantharidin biosynthesis during the adult phase. McCYP305a1 collaborates with its upstream gene McSTE24 in cantharidin biosynthesis, while McJHEH independently regulates cantharidin biosynthesis in males.
摘要：
斑潜素是一种有毒的防御物质，大多数水泡甲虫在攻击时会分泌。自古以来，它已被用于治疗许多复杂的疾病，最近作为抗癌剂重新受到欢迎。然而,斑驳素生物合成的详细机制尚未得到完全解决。在这项研究中,我们从萜类骨架途径克隆了McSTE24（编码STE24内肽酶），McCYP305a1（编码细胞色素P450，家族305）和McJHEH[编码亚家族A，多肽1和幼体激素（JH）环氧化物水解酶]与水泡甲虫Mylabriscichorii的JH合成/降解有关（Linnaeus，1758年，鞘翅目：Meloidae）。成年雄性发育阶段的表达模式分析显示，3种转录物的表达仅在斑驳素合成的高峰期（20-25天大）与斑驳素滴度密切相关。相比之下,在其他阶段,这些基因可能主要调节不同的生物过程。当RNA干扰双链RNA分别抑制3个基因的表达时，在McJHEH敲除后，男性和女性中观察到斑蒿苷产量显着降低，表明这3个基因可能主要有助于男性斑蒿苷的生物合成，但不是女性，而雌性可以自我合成少量的斑三素。这些发现支持了先前假设的成年阶段斑蒿苷生物合成中的性二态性。McCYP305a1与它的上游基因McSTE24合作进行斑三素的生物合成，而McJHEH独立调节男性斑蒿苷的生物合成。
