Chemical constraints, evolutionary novelties, and biochemical flexibility in detoxification strategies to plant defenses

Plants synthesize a diverse array of bioactive metabolites to deter herbivory. Their composition varies among plant species and families, reflecting plant adaptation to a broad spectrum of herbivores. In turn, herbivores have evolved multiple strategies to cope with these compounds, enabling them to exploit plant-based diets. Among these, detoxification is a key mechanism by which plant defense metabolites are enzymatically modified into less toxic or readily excreted products. While plant resistance traits and herbivore counteradaptations have been extensively studied in the context of plant–arthropod interactions, humans also consume a wide variety of plants and are consequently exposed to many of the same bioactive compounds. Here, we review and compare the biotransformation mechanisms employed by herbivorous arthropods and humans in response to three structurally and chemically distinct plant defense metabolites: nicotine, glucosinolates, and the most abundant tea catechin, epigallocatechin gallate (EGCG), to examine how similar chemical challenges are addressed by taxonomically non-related organisms. Nicotine illustrates conserved transformations performed by taxon-specific enzymes, while glucosinolate metabolism combines common glutathione-dependent conjugation with specialized innovations. Biotransformation of EGCG exemplifies divergent strategies used by humans and mites, where the latter gained a new strategy through the acquisition of horizontally transferred dioxygenases. Together, these examples suggest that plant defensive chemistry constrains the range of chemically feasible detoxification reactions, while evolution diversifies solutions through enzyme-family expansion, neofunctionalization, horizontal gene transfer, and microbial symbiosis.