Met基因在黏虫生殖中的功能分析

保幼激素(juvenile hormone, JH)是由咽侧体分泌的倍半萜类化合物,可以调控昆虫的很多生理过程,如发育、变态、生殖等。作为bHLH-PAS(helix-loop-helix-Per-ARNT-Sim)转录因子家族成员之一的methoprene-tolerant (Met)是JH的受体,在JH的信号传导过程中有非常重要的作用。本研究通过实时荧光定量PCR结合RNAi技术测定了沉默Met基因后黏虫Mythimna separata的Vg基因表达、卵巢发育和生殖行为,旨在探究Met基因在黏虫生殖过程中的功能。结果表明当Met基因沉默后,与卵巢发育密切相关的卵黄原蛋白(vitellogenin, Vg)基因表达量下调了50%,从而显著抑制了卵巢发育,并导致产卵显著延迟、产卵历期显著缩短,产卵量显著下降。结果表明Met基因是黏虫生殖发育过程中的关键受体基因,它通过调节后续Vg的表达和沉积,来达到控制卵巢发育,从而调控生殖作用。     

Virtual screening identifies a novel piperazine-based insect juvenile hormone agonist

Juvenile hormone (JH) agonists constitute a subclass of insect growth regulators and play important roles in insect pest management. In this work, a multi-step virtual screening program was executed to find novel JH agonists. A database of 5 million purchasable compounds was sequentially processed with three computational filters: (i) shape and chemical similarity as compared to known JH-active compounds; (ii) molecular docking simulations against a Drosophila JH receptor, methoprene-tolerant; and (iii) free energy calculation of ligand–receptor binding using a modified MM/PBSA (molecular mechanics/Poisson–Boltzmann surface area) protocol. The 11 candidates that passed the three filters were evaluated in a luciferase reporter assay, leading to the identification of a hit compound that contains a piperazine ring system (EC₅₀=870 nM). This compound is structurally dissimilar to known JH agonists and synthetically easy to access; therefore, it is a promising starting point for further structure optimization.