Chemical Punch Packed in Venoms Makes Centipedes Excellent Predators

Abstract

Centipedes are excellent predatory arthropods that inject venom to kill or immobilize their prey. Although centipedes have long been known to be venomous, their venoms remain largely unexplored. The chemical components responsible for centipede predation and the functional mechanisms are unknown. Twenty-six neurotoxin-like peptides belonging to ten groups were identified from the centipede venoms, Scolopendra subspinipes mutilans L. Koch by peptidomics combined with transcriptome analysis, revealing the diversity of neurotoxins. These neurotoxins each contain two to four intramolecular disulfide bridges, and in most cases the disulfide framework is different from that found in neurotoxins from the venoms of spiders, scorpions, marine cone snails, sea anemones, and snakes (5S animals). Several neurotoxins contain potential insecticidal abilities, and they are found to act on voltage-gated sodium, potassium, and calcium channels, respectively. Although these neurotoxins are functionally similar to the disulfiderich neurotoxins found in the venoms of 5S animals in that they modulate the activity of voltage-gated ion channels, in almost all cases the primary structures of the centipede venom peptides are unique. This represents an interesting case of convergent evolution in which different venomous animals have evolved different molecular strategies for targeting the same ion channels in prey and predators. Moreover, the high level of biochemical diversity revealed in this study suggests that centipede venoms might be attractive subjects for prospecting and screening for peptide candidates with potential pharmaceutical or agrochemical applications. Molecular & Cellular

Discovery of a selective Na V 1.7 inhibitor from centipede venom with analgesic efficacy exceeding morphine in rodent pain models

“…In this study we examined centipede venom as a potential source of selective Na V 1.7 inhibitors because we previously demonstrated that these venoms are replete with ion channel modulators (14). We described the purification and functional characterization of a unique peptide (Ssm6a) with potent analgesic properties from venom of the centipede S. subspinipes mutilans.…”

“…S1) indicates that the six cysteine residues form three disulfide bonds. A BLAST search of the protein/DNA sequence databases revealed that Ssm6a is not similar to any known peptide or protein, except for ∼40% sequence identity with κ-SLPTX-Ssm1a that we recently isolated from the venom of the same centipede (14).…”

“…There are ∼3,300 extant species of centipedes, yet the venom of only a handful has been studied in any detail. We recently demonstrated that the venom of the Chinese red-headed centipede Scolopendra subspinipes mutilans is replete with unique, disulfide-rich peptides that potently modulate the activity of mammalian voltage-gated ion channels (14), and therefore we decided to explore this venom as a potential source of Na V 1.7 inhibitors. We describe the purification from this venom of a highly selective inhibitor of Na V 1.7 that is a more effective analgesic than morphine in rodent pain models.…”

“…Centipedes were one of the first terrestrial taxa to use venom as a predation strategy, and they have adapted to capture a wide variety of prey, including insects, fish, molluscs, amphibians, reptiles, and even mammals (13,14). The centipede venom apparatus, which is unique and bears little resemblance to that of other arthropods, evolved by modification of the first pair of walking legs into a set of pincerlike claws (forcipules) (13).…”

Centipede venoms as a source of drug leads

“…The venom peptides, which are of most interest from a drug discovery perspective, are extraordinarily diverse [25,[27][28][29][30][31][32]. Undheim et al [30] classified centipede venom peptides into 31 phylogenetically distinct families of scutigerotoxins (SCUTX1-3) and scoloptoxins ( .…”