Enlighting the toxinological dark matter of spider venom enzymes

Spiders produce highly adapted venoms featuring a complex mixture of biomolecules used mainly for hunting and defense. The most prominent components are peptidic neurotoxins, which have been the focus of research and drug development, whereas venom enzymes have been largely neglected. Nevertheless, investigation of venom enzymes not only reveals insights into their biological functions, but also provides templates for future industrial applications. Here we compared spider venom enzymes contained in the VenomZone database and in other publicly available proteo-transcriptomic datasets. We found extensive discrepancies between these sources, revealing a previously unrecognized abundance and diversity of venom enzymes. Furthermore, we assigned the reported enzymes to cellular processes and known venom functions, including toxicity, prey pre-digestion, venom preservation, venom component activation, and venom spreading factors. Our study reveals a gap between databases and publications in terms of enzyme coverage which impedes development of new applications based on the rich and diverse spectrum of enzymes contained in spider venom.