第十五届海洋药物学术年会暨2021国际海洋药物研讨会

45 / 2021-10-09 21:49:54

High conotoxins diversity in Conus striatus revealed through analysis of transcriptome using two high-throughput sequencing platforms

cone snail; Conus striatus; transcriptomics; conotoxin; radular gland; venom duct; venom gland; salivary gland

Marine cone snail venoms represent a vast library of bioactive peptides and proteins with proven potential, not only as research tools but also as drug leads and therapeutics, whose consist of mixtures of hundreds of conotoxins with a diverse array of molecular targets, including voltage and ligand gated ion channels, G-protein coupled receptors and neurotransmitter transporters. In this study, we performed high-throughput transcriptome sequencing to obtain putative conotoxins transcripts from different organs of the piscivorous cone snail, Conus striatus, including the radular gland, venom duct, venom gland and salivary gland. For the first time in cone snail, the venom transcriptomes of C. striatus were sequenced by combining, and a comprehensive library of 429 conotoxin transcripts was constructed. The total numbers of identified conotoxins precursors and hormones form Illumina and Sequel platforms were 82 and 367 belonging to 20 known gene superfamilies and two new conotoxin groups, the great diversity so far observed from a transcriptome. Most of the identified peptides exhibited divergence from the known conotoxins and some contained cysteine frameworks observed for the first time in cone snails. Conotoxins from A and O superfamilies were the most abundant in transcript number and transcription level, suggesting their critical roles in the venom functions of these fish-hunting cone snails. We also identified several enzymes involved in post-translational modification of conotoxins and some proteins involved in efficient delivery of the conotoxins to prey, which may shed light on the fundamental mechanisms for the generation of these important conotoxins within the organs of C. striatus. In addition, it appeared that most of the identified conotoxins were synthesized in the venom duct, for the identified conotoxins in the venom duct at relatively high levels, and a portion of conotoxins were identified in the other organs and at low levels. Therefore, we have demonstrated an efficient combination of methods to mine Conus and generate a library of sequences encoding bioactive peptides, proving the diversity of conotoxins in different organs which will make a greater contribution to the discovery of new conotoxins for future drug development.