Lepidopteran HMG-CoA reductase is a potential selective target for pest control

PeerJ. 2017 Jan 19:5:e2881. doi: 10.7717/peerj.2881. eCollection 2017.

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.

Keywords: HMG-CoA reductase; Selective insecticide target; Sequence alignment; Statins; Structural comparison.

Grants and funding

This work was supported by a grant from the National Natural Science Foundation of China (No. 21402122). It was also supported by Natural Science Foundation of Shanghai (No. 14ZR1440600), and the Scientific Research Foundation for the Returned Overseas Chinese Scholars, Ministry of Education of PRC (No. ZX2015-9). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.