Properties and functions of farnesyl diphosphate synthase paralogs in the Lepidoptera

传统的化学杀虫剂往往对非目标生物体，包括人类产生有害影响。因此，限制其在林业和农业中使用的压力越来越大。目前为发现更安全的替代品而实施的战略之一涉及开发破坏特定于一组昆虫的生化过程的分子，因为这种分子不太可能对非目标生物体产生严重的负面影响。然而，在开发这些分子之前，必须首先确定哪些生理和生化过程容易受到致命的破坏，并对潜在的机制有全面的了解，包括对将被破坏的蛋白质（通常是酶或受体）的表征。目前的研究集中在一种酶（法呢基二磷酸合酶或FPPS），在几个生理过程中发挥着关键作用，包括昆虫的变态和繁殖的调节。因此，这种酶是合成“保幼激素”（JH）所必需的，JH是一种控制昆虫形态发生和卵成熟的萜类化合物。JH生物合成是一个合适的目标中断，因为它的抑制有深远的影响，这两个过程。在一组被称为鳞翅目（毛虫，蛾，蝴蝶）的昆虫中，我们已经分离出两种非常不同的FPPS，表现出将它们与这种酶的其他“常规”形式区分开来的特征。出于这个原因，开发对鳞翅目FPPS特异的抑制剂（即，而对其它生物体中的相应酶没有或几乎没有影响）似乎是可能的。然而，我们必须首先更好地了解这两种FPPS如何相互作用，确定它们各自在JH生物合成和其他生理过程中的作用，并开发有关其独特结构特征的知识，以便我们可以设计针对它们的抑制剂。这种抑制剂可以形成新的鳞翅目特异性杀虫剂的基础。

Conventional chemical insecticides tend to have detrimental impacts on non-target organisms, including humans. For this reason, there is increasing pressure to limit their use in forestry and agriculture. One of the strategies currently implemented for the discovery of safer alternatives involves the development of molecules that disrupt biochemical processes that are specific to a group of insects, because such molecules are unlikely to have serious negative effects on non-target organisms. Before developing these molecules, however, one must first identify physiological and biochemical processes that are amenable to being fatally disrupted, and develop a thorough knowledge of the underlying mechanisms, including a characterization of the proteins (typically enzymes or receptors) that will be targeted for disruption. The present research focuses on an enzyme (farnesyl diphosphate synthase or FPPS) that plays a critical role in several physiological processes, including the regulation of metamorphosis and reproduction in insects. As such, this enzyme is essential to the synthesis of "juvenile hormone" (JH), a terpenoid compound that controls insect morphogenesis and egg maturation. JH biosynthesis is an appropriate target for disruption because its inhibition has profound effects on these two processes. In a group of insects known as the Lepidoptera (caterpillars, moths, butterflies), we have isolated two very distinct FPPSs, exhibiting features that set them apart from other, "conventional" forms of this enzyme. For this reason, the development of inhibitors that are specific to lepidopteran FPPSs (i.e., with no or little effect on the corresponding enzyme in other organisms) appears possible. However, we must first acquire a better understanding of how these two FPPSs interact with one another, identify their respective roles in JH biosynthesis and other physiological processes, and develop knowledge about their unique structural features, so that we can design inhibitors that are specific to them. Such inhibitors could form the basis of novel, lepidoptera-specific insecticides.