Spider-derived peptides with insecticidal, antimicrobial and/or cytolytic activities, also known as spider venom antimicrobial peptides (AMPs), can be found in the venoms of RTA-clade spiders. They show translational potential as therapeutic leads. A set of 52 AMPs has been described in the Chinese wolf spider (Lycosa shansia), and many have been shown to exhibit antibacterial effects. Here we explored the potential to enhance their antimicrobial activity using bioengineering. We generated a panel of artificial derivatives of an A-family peptide and screened their activity against selected microbial pathogens, vertebrate cells and insects. In several cases, we increased the antimicrobial activity of the derivatives while retaining the low cytotoxicity of the parental molecule. Furthermore, we injected the peptides into adult Drosophila suzukii and found no evidence of insecticidal effects, confirming the low levels of toxicity. Our data therefore suggest that spider venom linear peptides naturally defend the venom gland against microbial colonization and can be modified into more potent antimicrobial agents that could help to battle infectious diseases in the future.

Bioassays are the main tool to decipher bioactivities from natural resources thus their selection and quality are critical for optimal bioprospecting. They are used both in the early stages of compounds isolation/purification/identification, and in later stages to evaluate their safety and efficacy. In this review, we provide a comprehensive overview of the most common bioassays used in the discovery and development of new bioactive compounds with a focus on marine bioresources. We present a comprehensive list of practical considerations for selecting appropriate bioassays and discuss in detail the bioassays typically used to explore antimicrobial, antibiofilm, cytotoxic, antiviral, antioxidant, and anti-ageing potential. The concept of quality control and bioassay validation are introduced, followed by safety considerations, which are critical to advancing bioactive compounds to a higher stage of development. We conclude by providing an application-oriented view focused on the development of pharmaceuticals, food supplements, and cosmetics, the industrial pipelines where currently known marine natural products hold most potential. We highlight the importance of gaining reliable bioassay results, as these serve as a starting point for application-based development and further testing, as well as for consideration by regulatory authorities.

The incorporation of bromine, iodine or fluorine into the tricyclic core structure of thiaplakortone A (1), a potent antimalarial marine natural product, is reported. Although yields were low, it was possible to synthesise a small nine-membered library using the previously synthesised Boc-protected thiaplakortone A (2) as a scaffold for late-stage functionalisation. The new thiaplakortone A analogues (3-11) were generated using N-bromosuccinimide, N-iodosuccinimide or a Diversinate™ reagent. The chemical structures of all new analogues were fully characterised by 1D/2D NMR, UV, IR and MS data analyses. All compounds were evaluated for their antimalarial activity against Plasmodium falciparum 3D7 (drug-sensitive) and Dd2 (drug-resistant) strains. Incorporation of halogens at positions 2 and 7 of the thiaplakortone A scaffold was shown to reduce antimalarial activity compared to the natural product. Of the new compounds, the mono-brominated analogue (compound 5) displayed the best antimalarial activity with IC50 values of 0.559 and 0.058 μM against P. falciparum 3D7 and Dd2, respectively, with minimal toxicity against a human cell line (HEK293) observed at 80 μM. Of note, the majority of the halogenated compounds showed greater efficacy against the P. falciparum drug-resistant strain.

Venoms are complex chemical arsenals that have evolved independently many times in the animal kingdom. Venoms have attracted the interest of researchers because they are an important innovation that has contributed greatly to the evolutionary success of many animals, and their medical relevance offers significant potential for drug discovery. During the last decade, venom research has been revolutionized by the application of systems biology, giving rise to a novel field known as venomics. More recently, biotechnology has also made an increasing impact in this field. Its methods provide the means to disentangle and study venom systems across all levels of biological organization and, given their tremendous impact on the life sciences, these pivotal tools greatly facilitate the coherent understanding of venom system organization, development, biochemistry, and therapeutic activity. Even so, we lack a comprehensive overview of major advances achieved by applying biotechnology to venom systems. This review therefore considers the methods, insights, and potential future developments of biotechnological applications in the field of venom research. We follow the levels of biological organization and structure, starting with the methods used to study the genomic blueprint and genetic machinery of venoms, followed gene products and their functional phenotypes. We argue that biotechnology can answer some of the most urgent questions in venom research, particularly when multiple approaches are combined together, and with other venomics technologies.

The relative lack of marine venom pharmaceuticals can be anecdotally attributed to difficulties in working with venomous marine animals, including how to maintain venom bioactivity during extraction and purification. The primary aim of this systematic literature review was to examine the key factors for consideration when extracting and purifying jellyfish venom toxins to maximise their effectiveness in bioassays towards the characterisation of a single toxin.An up-to-date database of 119 peer-reviewed research articles was established for all purified and semi-purified venoms across all jellyfish, including their level of purification, LD50, and the types of experimental toxicity bioassay used (e.g., whole animal and cell lines). We report that, of the toxins successfully purified across all jellyfish, the class Cubozoa (i.e., Chironex fleckeri and Carybdea rastoni) was most highly represented, followed by Scyphozoa and Hydrozoa. We outline the best practices for maintaining jellyfish venom bioactivity, including strict thermal management, using the \"autolysis\" extraction method and two-step liquid chromatography purification involving size exclusion chromatography. To date, the box jellyfish C. fleckeri has been the most effective jellyfish venom model with the most referenced extraction methods and the most isolated toxins, including CfTX-A/B. In summary, this review can be used as a resource for the efficient extraction, purification, and identification of jellyfish venom toxins.

The venoms of ants (Formicidae) are a promising source of novel bioactive molecules with potential for clinical and agricultural applications. However, despite the rich diversity of ant species, only a fraction of this vast resource has been thoroughly examined in bioprospecting programs. Previous studies focusing on the venom of Central European ants (subfamily Myrmicinae) identified a number of short linear decapeptides and nonapeptides resembling antimicrobial peptides (AMPs). Here, we describe the in silico approach and bioactivity profiling of 10 novel AMP-like peptides from the fellow Central European myrmicine ants Myrmica rubra and Myrmica ruginodis. Using the sequences of known ant venom peptides as queries, we screened the venom gland transcriptomes of both species. We found transcripts of nine novel decapeptides and one novel nonapeptide. The corresponding peptides were synthesized for bioactivity profiling in a broad panel of assays consisting of tests for cytotoxicity as well as antiviral, insecticidal, and antimicrobial activity. U-MYRTX-Mrug5a showed moderately potent antimicrobial effects against several bacteria, including clinically relevant pathogens such as Listeria monocytogenes and Staphylococcus epidermidis, but high concentrations showed negligible cytotoxicity. U-MYRTX-Mrug5a is, therefore, a probable lead for the development of novel peptide-based antibiotics.

In order to further expand the NatureBank open access compound library, chemical investigations of the Australian marine sponge, Ianthella basta, were undertaken since UHPLC-MS analysis of the extract from this sponge indicated the presence of a new alkaloid. Large-scale extraction and mass-directed isolation studies on the CH2Cl2/MeOH I. basta extract resulted in the purification of a new bromotyrosine-derived alkaloid, 5-debromopurealidin H (1), along with the known marine natural product, ianthesine E (2). The chemical structure of the new compound was determined following detailed spectroscopic and spectrometric data analysis. These two compounds (1 and 2) along with seven previously reported marine bromotyrosine alkaloids from the NatureBank open access library, which included psammaplysins F (3) and H (4), bastadins 4 (5), 8 (6) and 13 (7), aerothionin (8) and hexadellin A (9), were evaluated for their nematocidal activity against exsheathed third-stage larvae of Haemonchus contortus, a highly pathogenic parasite of ruminants. Of the nine compounds, bastadin 8 (6), hexadellin A (9) and bastadin 4 (5) showed inhibition towards larval motility after 72 h of exposure with IC50 values of 1.6 µM, 10.0 µM and 33.3 µM, respectively.

Despite its low prevalence, pancreatic cancer (PC) is one of the deadliest, typically characterised as silent in early stages and with a dramatically poor prognosis when in its advanced stages, commonly associated with a high degree of metastasis. Many efforts have been made in pursuing innovative therapeutical approaches, from the search for new cytotoxic drugs and other bioactive compounds, to the development of more targeted approaches, including improved drug delivery devices. Marine biotechnology has been contributing to this quest by providing new chemical leads and materials originating from different organisms. In this review, marine biodiscovery for PC is addressed, particularly regarding marine invertebrates (namely sponges, molluscs, and bryozoans), seaweeds, fungi, and bacteria. In addition, the development of biomaterials based on marine-originating compounds, particularly chitosan, fucoidan, and alginate, for the production of advanced cancer therapies, is also discussed. The key role that drug delivery can play in new cancer treatments is highlighted, as therapeutical outcomes need to be improved to give further hope to patients.

As the traditional use of non-human genetic resources in research and development is increasingly ceded to computerised research activities, current frameworks for access and benefit-sharing face an impending identity crisis. The absence of international consensus on the regulation of digital sequence information presents a critical point of social division between the Global North and Global South, whereby a culture of \"open data\" promises immeasurable opportunity in high-income nations and threatens a wave of digital bio-piracy for vulnerable communities. This article critically evaluates these problems and considers solutions which draw on Indigenous Data Sovereignty principles. To do so, it uses the recent experience in Queensland to explore how the law might reconcile and balance these competing interests. Insofar as Queensland is one of the most mega biodiverse regions on earth, boasts a globally competitive life sciences sector, and has a vibrant and longstanding Indigenous population, it offers a unique case study.

The genus Aeromonas comprises Gram-negative bacilli widely distributed in aquatic habitats that can also be found in the terrestrial environment and in close association with humans and animals. Aeromonas spp. are particularly versatile bacteria, with high genomic plasticity and notable capacity to adapt to different environments and extreme conditions. On account of being mostly associated with their pathogenic potential, research on the biotechnological potentialities of Aeromonas spp. is considerably scarce when compared to other bacterial groups. Nonetheless, studies over the years have been hinting at several interesting hidden potentialities in this bacterial group, especially with the recent advances in whole-genome sequencing, unveiling Aeromonas spp. as interesting candidates for the discovery of novel industrial biocatalysts, bioremediation strategies, and biopolyester production. In this context, the present study aims to provide an overview of the main biotechnological applications reported in the genus Aeromonas and provide new insights into the further exploration of these frequently overlooked, yet fascinating, bacteria.