A Hydrolase-Rich Venom Beyond Neurotoxins: Integrative Functional Proteomic and Immunoreactivity Analyses Reveal Novel Peptides in the Amazonian Scorpion Brotheas amazonicus
Abstract
The scorpion family Buthidae, renowned for its neurotoxin-rich venoms, dominates toxinology, while non-buthid venoms remain largely unexplored. Here, we present a comprehensive proteomic and biochemical characterization of the Amazonian chactid scorpion Brotheas amazonicus venom (BamazV), with emphasis on molecular complexity, proteolytic processing, and peptide diversity. Using an integrative venomics approach that combines molecular mass-based fractionation, reversed-phase chromatography, high-resolution mass spectrometry, N-terminal sequencing, and functional and immunological analyses, we reveal an unexpectedly complex venom profile enriched in high-molecular-weight components and extensively processed peptides, with more than 40 venom peptides sequenced by MS/MS and Edman degradation. The data provide evidence for non-canonical proteolytic events, including the generation of peptides from precursor regions not classically associated with mature venom components. In contrast to the venom of Tityus serrulatus, BamazV displays a “hydrolase-rich, neurotoxin-poor” profile, featuring a catalytically active Group III phospholipase A2 (BamazPLA2), a highly active hyaluronidase, metalloproteases, low-mass peptides, and potassium channel toxins. Our results suggest a hydrolytic prey-subjugation strategy, and limited cross-reactivity with commercial antivenom highlighted its distinct structural landscape. Overall, this study advances the understanding of venom evolution and proteolytic diversification in underexplored scorpion lineages, positioning B. amazonicus as a valuable model for investigating alternative venom strategies and identifying novel biotechnological scaffolds.
Wiezel, G. A., Bordon, K. D., Martins, J. G., Custódio, V. I., Matsuno, A. K., Procópio, R. E., & Arantes, E. C. (2026). A Hydrolase-Rich Venom Beyond Neurotoxins: Integrative Functional Proteomic and Immunoreactivity Analyses Reveal Novel Peptides in the Amazonian Scorpion Brotheas amazonicus.
International Journal of Molecular Sciences,
27(3), 1475.
https://doi.org/10.3390/ijms27031475
