Transcriptomes and Proteomes of Marine Venomous Animals as Source for Drug Discovery

A special issue of Marine Drugs (ISSN 1660-3397).

Deadline for manuscript submissions: closed (31 March 2022) | Viewed by 14919

Special Issue Editors


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Guest Editor
Departamento de Biodiversidad y Biología Evolutiva, Museo Nacional de Ciencias Naturales (MNCN-CSIC), José Gutiérrez Abascal, 2, 28006 Madrid, Spain
Interests: evolutionary genomics; comparative transcriptomics; phylogenomics; venomics; gastropods

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Guest Editor
Department of Material Science and Metallurgy Engineering and Inorganic Chemistry, Universidad de Cadiz, Cadiz, Spain
Interests: organometallic chemistry; inorganic chemistry; homogeneous catalysis; organic synthesis; NMR spectroscopy; venomics; marine drugs; marine toxins; systematics (taxonomy)

Special Issue Information

Dear Colleagues,

Venomics integrates high-throughput proteomics, transcriptomics, and genomics to accelerate the large-scale study of venoms of peptidic nature and the discovery of novel therapeutic drugs. Every venomous marine species produces a unique cocktail, whose protein components can be characterized in detail using high-throughput techniques. By comparing gene family contents, expressed transcripts, and functional (post-translationally modified) protein products, it is possible to elucidate the different molecular mechanisms responsible for producing the great diversity of venoms. By comparing venom mixtures within a phylogenetic framework, it is also possible to distinguish those components that are shared between species (and determine whether they are derived from a common ancestor or convergent) from those that are evolutionary innovations of a particular taxon.

This Special Issue of Marine Drugs aims at gathering original research articles that contribute to catalogue the existing great diversity of marine venoms, and to understand how this diversity is generated and evolves. Attention is focused on the use of combined transcriptomic and proteomic tools to reach this ultimate goal.

Prof. Dr. Rafael Zardoya
Prof. Dr. Manuel Jiménez-Tenorio
Guest Editors

Manuscript Submission Information

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Keywords

  • trancriptomics
  • proteomics
  • evolution
  • venoms
  • drug discovery
  • mass spectrometry
  • next-generation sequencing

Published Papers (5 papers)

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Research

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19 pages, 8325 KiB  
Article
Endogenous Fluorescent Proteins in the Mucus of an Intertidal Polychaeta: Clues for Biotechnology
by Ana P. Rodrigo, Ana Lopes, Ricardo Pereira, Sandra I. Anjo, Bruno Manadas, Ana R. Grosso, Pedro V. Baptista, Alexandra R. Fernandes and Pedro M. Costa
Mar. Drugs 2022, 20(4), 224; https://doi.org/10.3390/md20040224 - 25 Mar 2022
Cited by 3 | Viewed by 2458
Abstract
The vast ocean holds many unexplored organisms with unique adaptive features that enable them to thrive in their environment. The secretion of fluorescent proteins is one of them, with reports on the presence of such compounds in marine annelids being scarce. The intertidal [...] Read more.
The vast ocean holds many unexplored organisms with unique adaptive features that enable them to thrive in their environment. The secretion of fluorescent proteins is one of them, with reports on the presence of such compounds in marine annelids being scarce. The intertidal Eulalia sp. is an example. The worm secretes copious amounts of mucus, that when purified and concentrated extracts, yield strong fluorescence under UV light. Emission has two main maxima, at 400 nm and at 500 nm, with the latter responsible for the blue–greenish fluorescence. Combining proteomics and transcriptomics techniques, we identified ubiquitin, peroxiredoxin, and 14-3-3 protein as key elements in the mucus. Fluorescence was found to be mainly modulated by redox status and pH, being consistently upheld in extracts prepared in Tris-HCl buffer with reducing agent at pH 7 and excited at 330 nm. One of the proteins associated with the fluorescent signal was localized in secretory cells in the pharynx. The results indicate that the secretion of fluorescent proteinaceous complexes can be an important defense against UV for this dweller. Additionally, the internalization of fluorescent complexes by ovarian cancer cells and modulation of fluorescence of redox status bears important considerations for biotechnological application of mucus components as markers. Full article
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21 pages, 2087 KiB  
Article
Comparative Venomics of the Cryptic Cone Snail Species Virroconus ebraeus and Virroconus judaeus
by José Ramón Pardos-Blas, Manuel J. Tenorio, Juan Carlos G. Galindo and Rafael Zardoya
Mar. Drugs 2022, 20(2), 149; https://doi.org/10.3390/md20020149 - 17 Feb 2022
Cited by 5 | Viewed by 2797
Abstract
The venom duct transcriptomes and proteomes of the cryptic cone snail species Virroconus ebraeus and Virroconus judaeus were obtained and compared. The most abundant and shared conotoxin precursor superfamilies in both species were M, O1, and O2. Additionally, three new putative conotoxin precursor [...] Read more.
The venom duct transcriptomes and proteomes of the cryptic cone snail species Virroconus ebraeus and Virroconus judaeus were obtained and compared. The most abundant and shared conotoxin precursor superfamilies in both species were M, O1, and O2. Additionally, three new putative conotoxin precursor superfamilies (Virro01-03) with cysteine pattern types VI/VII and XVI were identified. The most expressed conotoxin precursor superfamilies were SF-mi2 and M in V. ebraeus, and Cerm03 and M in V. judaeus. Up to 16 conotoxin precursor superfamilies and hormones were differentially expressed between both species, and clustered into two distinct sets, which could represent adaptations of each species to different diets. Finally, we predicted, with machine learning algorithms, the 3D structure model of selected venom proteins including the differentially expressed Cerm03 and SF-mi2, an insulin type 3, a Gastridium geographus GVIA-like conotoxin, and an ortholog to the Pionoconus magus ω-conotoxin MVIIA (Ziconotide). Full article
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9 pages, 889 KiB  
Communication
Identification of Novel Conotoxin Precursors from the Cone Snail Conus spurius by High-Throughput RNA Sequencing
by Roberto Zamora-Bustillos, Mario Alberto Martínez-Núñez, Manuel B. Aguilar, Reyna Cristina Collí-Dula and Diego Alfredo Brito-Domínguez
Mar. Drugs 2021, 19(10), 547; https://doi.org/10.3390/md19100547 - 28 Sep 2021
Cited by 6 | Viewed by 1948
Abstract
Marine gastropods of the genus Conus, comprising more than 800 species, have the characteristic of injecting worms and other prey with venom. These conopeptide toxins, highly diverse in structure and action, are highly potent and specific for their molecular targets (ion channels, [...] Read more.
Marine gastropods of the genus Conus, comprising more than 800 species, have the characteristic of injecting worms and other prey with venom. These conopeptide toxins, highly diverse in structure and action, are highly potent and specific for their molecular targets (ion channels, receptors, and transporters of the prey’s nervous system), and thus are important research tools and source for drug discovery. Next-generation sequencing technologies are speeding up the discovery of novel conopeptides in many of these species, but only limited information is available for Conus spurius, which inhabits sandy mud. To search for new precursor conopeptides, we analyzed the transcriptome of the venous ducts of C. spurius and identified 55 putative conotoxins. Seven were selected for further study and confirmed by Sanger sequencing to belong to the M-superfamily (Sr3.M01 and Sr3.M02), A-superfamily (Sr1.A01 and Sr1.A02), O-superfamily (Sr15.O01), and Con-ikot-ikot (Sr21.CII01 and Sr22.CII02). Six of these have never been reported. To our knowledge, this report is the first to use high-throughput RNA sequencing for the study of the diversity of C. spurius conotoxins. Full article
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14 pages, 21186 KiB  
Article
Diversity of Conopeptides and Conoenzymes from the Venom Duct of the Marine Cone Snail Conus bayani as Determined from Transcriptomic and Proteomic Analyses
by Rajesh Rajaian Pushpabai, Carlton Ranjith Wilson Alphonse, Rajasekar Mani, Deepak Arun Apte and Jayaseelan Benjamin Franklin
Mar. Drugs 2021, 19(4), 202; https://doi.org/10.3390/md19040202 - 03 Apr 2021
Cited by 3 | Viewed by 3238
Abstract
Marine cone snails are predatory gastropods characterized by a well-developed venom apparatus and highly evolved hunting strategies that utilize toxins to paralyze prey and defend against predators. The venom of each species of cone snail has a large number of pharmacologically active peptides [...] Read more.
Marine cone snails are predatory gastropods characterized by a well-developed venom apparatus and highly evolved hunting strategies that utilize toxins to paralyze prey and defend against predators. The venom of each species of cone snail has a large number of pharmacologically active peptides known as conopeptides or conotoxins that are usually unique in each species. Nevertheless, venoms of only very few species have been characterized so far by transcriptomic approaches. In this study, we used transcriptome sequencing technologies and mass spectrometric methods to describe the diversity of venom components expressed by a worm-hunting species, Conus bayani. A total of 82 conotoxin sequences were retrieved from transcriptomic data that contain 54 validated conotoxin sequences clustered into 21 gene superfamilies including divergent gene family, 17 sequences clustered to 6 different conotoxin classes, and 11 conotoxins classified as unassigned gene family. Seven new conotoxin sequences showed unusual cysteine patterns. We were also able to identify 19 peptide sequences using mass spectrometry that completely overlapped with the conotoxin sequences obtained from transcriptome analysis. Importantly, herein we document the presence of 16 proteins that include five post-translational modifying enzymes obtained from transcriptomic data. Our results revealed diverse and novel conopeptides of an unexplored species that could be used extensively in biomedical research due to their therapeutic potentials. Full article
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16 pages, 5196 KiB  
Review
Biomedical Potential of the Neglected Molluscivorous and Vermivorous Conus Species
by Yihe Zhao and Agostinho Antunes
Mar. Drugs 2022, 20(2), 105; https://doi.org/10.3390/md20020105 - 27 Jan 2022
Cited by 6 | Viewed by 3409
Abstract
Within the Conidae family, the piscivorous Conus species have been a hotspot target for drug discovery. Here, we assess the relevance of Conus and their other feeding habits, and thus under distinctive evolutionary constraints, to highlight the potential of neglected molluscivorous and vermivorous [...] Read more.
Within the Conidae family, the piscivorous Conus species have been a hotspot target for drug discovery. Here, we assess the relevance of Conus and their other feeding habits, and thus under distinctive evolutionary constraints, to highlight the potential of neglected molluscivorous and vermivorous species in biomedical research and pharmaceutical industry. By singling out the areas with inadequate Conus disquisition, such as the Tamil Nadu Coast and the Andaman Islands, research resources can be expanded and better protected through awareness. In this study, 728 Conus species and 190 species from three other genera (1 from Californiconus, 159 from Conasprella and 30 from Profundiconus) in the Conidae family are assessed. The phylogenetic relationships of the Conidae species are determined and their known feeding habits superimposed. The worm-hunting species appeared first, and later the mollusc- and fish-hunting species were derived independently in the Neogene period (around 23 million years ago). Interestingly, many Conus species in the warm and shallow waters become polyphagous, allowing them to hunt both fish and worms, given the opportunities. Such newly gained trait is multi originated. This is controversial, given the traditional idea that most Conus species are specialized to hunt certain prey categories. However, it shows the functional complexity and great potential of conopeptides from some worm-eating species. Pharmaceutical attempts and relevant omics data have been differentially obtained. Indeed, data from the fish-hunting species receive strong preference over the worm-hunting ones. Expectedly, conopeptides from the fish-hunting species are believed to include the most potential candidates for biomedical research. Our work revisits major findings throughout the Conus evolution and emphasizes the importance of increasing omics surveys complemented with further behavior observation studies. Hence, we claim that Conus species and their feeding habits are equally important, highlighting many places left for Conus exploration worldwide. We also discuss the Conotoxin drug discovery potentials and the urgency of protecting the bioresources of Conus species. In particular, some vermivorous species have demonstrated great potential in malaria therapy, while other conotoxins from several worm- and mollusc-eating species exhibited explicit correlation with SARS-CoV-2. Reclaiming idle data with new perspectives could also promote interdisciplinary studies in both virological and toxicological fields. Full article
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