Sajitha T P, Manjunatha B L, Siva R, Gogna Navdeep, Dorai Kavita, Ravikanth G, Uma Shaanker R
Department of Plant Biotechnology, School of Biosciences and Technology, Vellore Institute of Technology, Vellore, Tamilnadu, 632014, India.
Department of Crop Physiology and School of Ecology and Conservation, University of Agricultural Sciences, GKVK, Bangalore, Karnataka, 560065, India.
J Chem Ecol. 2018 Jun;44(6):611-620. doi: 10.1007/s10886-018-0960-2. Epub 2018 May 25.
Camptothecin (CPT), a monoterpene indole alkaloid, is a potent inhibitor of eukaryotic topoisomerase I (Top 1). Because of this property, several derivatives of CPT are widely used as chemotherapeutic agents. The compound is produced by several plant species, including Nothapodytes nimmoniana (Family: Icacinaceae) presumably as a deterrent to insect pests. Here, we report, a lepidopteran larva, Lymantria sp. of Lymantriidae family which feeds voraciously on the leaves of N. nimmoniana, without any adverse consequences. Larval body weight and molting period were unaffected despite captive feeding of the larva with CPT enriched leaves. Mass spectrometric analysis indicated that nearly 46% of the ingested CPT was excreted while the rest was sequestered predominantly in the exuviae and setae (~35%). Although most of the CPT was in the parental form as found in the plant, traces of inactive, sulfated forms of CPT were recovered from the larva. Compared to that in plant, there were no critical mutations at the CPT binding domain of the insect's Top 1. The gut pH of the larva was alkaline (pH 10.0). The alkaline gut environment converts CPT from its active, lactone form to inactive, carboxylate form. It is likely that such conversion might help the larva to reduce the overall burden of CPT in its gut. We discuss the results in the context of the mechanisms of resistance adapted by insects to plant toxins.
喜树碱（CPT）是一种单萜吲哚生物碱，是真核拓扑异构酶I（Top 1）的有效抑制剂。由于这一特性，CPT的几种衍生物被广泛用作化疗药物。该化合物由几种植物产生，包括印度蛇根木（Nothapodytes nimmoniana，茶茱萸科），推测是作为一种害虫驱避剂。在此，我们报告一种鳞翅目幼虫，毒蛾科的舞毒蛾属（Lymantria sp.），它贪婪地取食印度蛇根木的叶子，却没有任何不良后果。尽管用富含CPT的叶子圈养喂食幼虫，但其幼虫体重和蜕皮期并未受到影响。质谱分析表明，摄入的CPT近46%被排泄，其余主要被隔离在蜕和刚毛中（约35%）。虽然大部分CPT以植物中发现的亲本形式存在，但从幼虫中回收了微量无活性的硫酸化CPT形式。与植物中的相比，昆虫Top 1的CPT结合结构域没有关键突变。幼虫的肠道pH呈碱性（pH 10.0）。碱性肠道环境将CPT从其活性内酯形式转化为无活性的羧酸盐形式。这种转化可能有助于幼虫减轻肠道中CPT的总体负担。我们在昆虫对植物毒素适应的抗性机制背景下讨论了这些结果。
