Insect Arylalkylamine N-Acetyltransferases as Potential Targets for Novel Insecticide Design.

Brian G O Flynn,David J Merkler,Aidan J Hawley

doi:10.21767/2471-8084.100053

Abstract

Crop protection against destructive pests has been at the forefront of recent agricultural advancements. Rapid adaptive evolution has led to insects becoming immune to the chemicals employed to quell their damage. Insecticide resistance is a serious problem that negatively impacts food production, food storage, human health, and the environment. To make matters more complicated are the strict regulations in place on insecticide development, driven by rising public concern relating to the harmful effects these chemicals have on the environment and on society. A key component to solving the problem of insecticide resistance, while keeping public welfare in mind, is the identification of novel insect-specific protein targets. One unexplored target for the development of new targeted insecticides are the insect arylalkylamine N-acetyltransferases (iAANATs). This group of enzymes, shown to be intrinsic in the development of the insect cuticle, is an untapped well of potential for target-specific inhibition, while offering enough variety to ensure protection for non-target enzymes. In this review, we highlight kinetic, genetic and bioinformatic data showing that the iAANATs are intriguing insecticide targets that should be specific only for particular insect pests. Such a pest-specific insecticide would minimize environmental harm by eliminating such non-discriminate attacks which have made insecticides such a highly regulated industry, and would have negligible toxicity to humans and other mammals.

Highlights

Ever-increasing insecticide resistance illustrates the uphill battle faced by the food and agricultural industries
In Diptera- specific insect arylalkylamine N-acetyltransferases (iAANATs), for example, many hydrophobic residues are replaced with residues containing nucleophilic groups and hydrogen bond acceptors that are not found in other iAANATs [14]
This suggests that by exploiting these catalytically relevant, yet insect-specific residues, it is possible to design compounds that bind to a specific iAANAT family, such as Diptera iAANAT or Coleoptera iAANAT, which would not bind to others, leaving non-targeted species unaffected

Summary

Introduction

Ever-increasing insecticide resistance illustrates the uphill battle faced by the food and agricultural industries. A variety of biogenic amine neurotransmitters serve as acetyl group acceptors, meaning that the iAANATs are involved in neurotransmitter inactivation and, may contribute to the regulation of neural signaling networks [11]. An iAANAT-targeted insecticide would disrupt neural signaling, but would inhibit cuticle development, decrease the structural stability, result in a non-conforming appearance (harming the insects' ability to mate), and diminish the cuticle-mediated protection against injury and infection.

Results

Conclusion