Abstract

As a consequence of the negative impacts on the environment of some insecticides, discovery of eco-friendly insecticides and target has received global attention in recent years. Sequence alignment and structural comparison of the rate-limiting enzyme HMG-CoA reductase (HMGR) revealed differences between lepidopteran pests and other organisms, which suggested insect HMGR could be a selective insecticide target candidate. Inhibition of JH biosynthesis in vitro confirmed that HMGR inhibitors showed a potent lethal effect on the lepidopteran pest Manduca sexta, whereas there was little effect on JH biosynthesis in Apis mellifera and Diploptera punctata. The pest control application of these inhibitors demonstrated that they can be insecticide candidates with potent ovicidal activity, larvicidal activity and insect growth regulatory effects. The present study has validated that Lepidopteran HMGR can be a potent selective insecticide target, and the HMGR inhibitors (especially type II statins) could be selective insecticide candidates and lead compounds. Furthermore, we demonstrated that sequence alignment, homology modeling and structural comparison may be useful for determining potential enzymes or receptors which can be eco-friendly pesticide targets.

Highlights

  • The traditional insecticides have made a major contribution to agriculture and health

  • The insect juvenile hormones (JHs) are methyl esters of farnesoic acid 10, 11-epoxide (JH III) and related compounds, which function in the regulation of a number of insect physiological processes in insects including embryogenesis, larval and adult development, metamorphosis, reproduction, diapause, migration, polymorphism, and metabolism (Nijhout, 1994)

  • The HMG-CoA reductase (HMGR) of M. sexta, A. mellifera and D. punctata were selected for the structural comparison

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Summary

Introduction

The traditional insecticides have made a major contribution to agriculture and health. As a result of improper use and the inherent shortcomings of some insecticides, many showed negative impacts on the ecological environment. How to predict and avoid potential ecological risk in the initial phase of insecticide discovery is a problem that has not been fully resolved to date. The insect juvenile hormones (JHs) are methyl esters of farnesoic acid 10, 11-epoxide (JH III) and related compounds, which function in the regulation of a number of insect physiological processes in insects including embryogenesis, larval and adult development, metamorphosis, reproduction, diapause, migration, polymorphism, and metabolism (Nijhout, 1994). JH biosynthesis proceeds in the corpora allata (CA) through the mevalonic acid (MVA) pathway, which insects share with most other organisms. HMG-CoA reductase (HMGR) has been postulated to be a key enzyme

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