Insect-derived Antimicrobial Peptides: Biochemical Mechanisms, Microbial Targets, and Synthetic Biology Applications

Abstract

Insects, which make up the largest portion of animal biodiversity on Earth, thrive in environments abundant with pathogenic microorganisms. Their survival is largely due to a highly effective innate immune system that compensates for their lack of adaptive immunity. A central element of this defence system is antimicrobial peptides (AMPs), which are small, usually positively charged, and amphipathic molecules capable of neutralizing a wide range of microbial pathogens. These AMPs exhibit significant variability in their sequences, structures, and mechanisms of action, targeting microbial membranes as well as intracellular components. Given the growing concern of antibiotic-resistant pathogens, insect AMPs have attracted attention as promising templates for new antimicrobial agents. Recent progress in synthetic biology offers tools to engineer AMPs with improved features such as enhanced stability, specificity, and delivery. However, the therapeutic and commercial application of insect AMPs faces several challenges, including susceptibility to proteolytic degradation, potential cytotoxicity, and high production costs, which must be addressed to fully realize their potential. This review discusses the diversity of insect AMPs, their microbial targets, biochemical and molecular mechanisms, synthetic biology strategies for their enhancement, and their applications in medicine, agriculture, and industry.