The Terebridae and teretoxins: Combining phylogeny and anatomy for concerted discovery of bioactive compounds

The conoideans (cone snails, terebrids, and turrids) are a hyperdiverse group of marine gastropods that prey on fish, worms, and other mollusks (Figure 1). Several conoidean lineages are characterized by specialized organs referred to as a venom apparatus that is used to subdue prey [1]. Analysis over the last three decades of venom toxins produced by various species in the genus Conus (cone snails), the most famous representative of this group, reveal a complex system of molecular compounds (see e.g. [2,3]). Each Conus species is able to produce 100-200 peptide toxins [4,5], making this genus, and by extension the whole Conoidea superfamily, one of the most promising groups for the discovery of natural peptide toxins together with snakes, spiders and scorpions.Within the conoideans, the auger snails, or the Terebridae, include approximately 300 to 350 described species [6,7]. The Terebridae, characterized by an elongated shell, are mostly sand-dwellers that live in shallow-waters near the tropics. Contrary to cone snails, terebrids have not attracted significant scientific attention, and comparatively little is known about their ecology and toxinology. Most of the main lineages of conoideans, including terebrids and conids, diverged at least in the early Paleocene [8]. Such an early separation would indicate toxins from terebrids could be highly divergent and unique, compare to toxins found in the genus Conus.Presented here is an overview of the emerging potential of terebrids and their peptide toxins. As terebrid toxins are closely related to cone snail toxins (conotoxins), what is known about the structural and functional diversity of conotoxins, and their application in pharmacology is first briefly reviewed. In addition, a comparison will be made of the traditional biochemical approach to peptide toxin discovery, and a novel multidisciplinary biodiversity first approach, termed the Concerted Discovery Strategy (CDS). CDS combines molecular and chemical techniqu