Abstract

Venomous molluscs (Superfamily Conoidea) comprise a substantial fraction of tropical marine biodiversity (>15,000 species). Prior characterization of cone snail venoms established that bioactive venom components used to capture prey, defend against predators and for competitive interactions were relatively small, structured peptides (10–35 amino acids), most with multiple disulfide crosslinks. These venom components (“conotoxins, conopeptides”) have been widely studied in many laboratories, leading to pharmaceutical agents and probes. In this review, we describe how it has recently become clear that to varying degrees, cone snail venoms also contain bioactive non-peptidic small molecule components. Since the initial discovery of genuanine as the first bioactive venom small molecule with an unprecedented structure, a broad set of cone snail venoms have been examined for non-peptidic bioactive components. In particular, a basal clade of cone snails (Stephanoconus) that prey on polychaetes produce genuanine and many other small molecules in their venoms, suggesting that this lineage may be a rich source of non-peptidic cone snail venom natural products. In contrast to standing dogma in the field that peptide and proteins are predominantly used for prey capture in cone snails, these small molecules also contribute to prey capture and push the molecular diversity of cone snails beyond peptides. The compounds so far characterized are active on neurons and thus may potentially serve as leads for neuronal diseases. Thus, in analogy to the incredible pharmacopeia resulting from studying venom peptides, these small molecules may provide a new resource of pharmacological agents.

Highlights

  • The venomous cone snails comprise a biodiverse lineage of marine gastropods (∼1,000 living species) that specialize on the spectrum of prey envenomated by each species

  • The venom is injected by extending a proboscis from the anterior gut, through a highly -specialized radular tooth that serves as a hypodermic needle (Kohn et al, 1999)

  • The gene structure that encodes this family of venom components is conserved; a large fraction of the peptides encoded by this gene superfamily share their general targeting specificity—these inhibit nicotinic acetylcholine receptors of various types (McIntosh et al, 1999)

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Summary

INTRODUCTION

The venomous cone snails comprise a biodiverse lineage of marine gastropods (∼1,000 living species) that specialize on the spectrum of prey (fish, other gastropod molluscs, or polychaete worms) envenomated by each species. The cone snails can be grouped into distinct clades, based on molecular phylogenetic data; these divisions generally correlate with the prey specialization of each

Cone Snail Small Molecules
Compound Number
BIOSYNTHESIS OF CONE SNAIL VENOM SMALL MOLECULES
PHARMACOLOGY OF CONE SNAIL VENOM SMALL MOLECULES
CONTEXT AND FUTURE DIRECTIONS
AUTHOR CONTRIBUTIONS

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