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Global efforts to eradicate malaria are threatened by multiple factors, particularly the emergence of antimalarial drug resistant strains of Plasmodium falciparum. Heat shock proteins (HSPs), particularly P. falciparum HSPs (PfHSPs), represent promising drug targets due to their essential roles in parasite survival and virulence across the various life cycle stages. Despite structural similarities between human and malarial HSPs posing challenges, there is substantial evidence for subtle differences that could be exploited for selective drug targeting. This review provides an update on the potential of targeting various PfHSP families (particularly PfHSP40, PfHSP70, and PfHSP90) and their interactions within PfHSP complexes as a strategy to develop new antimalarial drugs. In addition, the need for a deeper understanding of the role of HSP complexes at the host-parasite interface is highlighted, especially heterologous partnerships between human and malarial HSPs, as this opens novel opportunities for targeting protein-protein interactions crucial for malaria parasite survival and pathogenesis.

Covering: January to the end of December 2023 This review covers the literature published in 2023 for marine natural products (MNPs), with 582 citations (541 for the period January to December 2023) referring to compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, the submerged parts of mangroves and other intertidal plants. The emphasis is on new compounds (1220 in 340 papers for 2023), together with the relevant biological activities, source organisms and country of origin. Pertinent reviews, biosynthetic studies, first syntheses, and syntheses that led to the revision of structures or stereochemistries, have been included. An analysis of the progress in the study of prokaryote involvement in macro-invertebrate MNP production is discussed. [ABSTRACT FROM AUTHOR]

Olfactory lures are important pest control tools, being widely used to attract animals to detection devices, traps, and poisons. For small mammals, like commensal rodents, almost all lures are foods. For invertebrates, however, semiochemical lures predominate and have done so for decades. Semiochemical lures overcome the inherent limitations of food-based lures, such as their perishability and inconsistent odour properties, and poor performance when foods are abundant. They can also provide benefits like low cost, ease of handling, and in-field longevity. Semiochemical lures for rodents would be a major advance, like that achieved for invertebrate monitoring and control, but their discovery has been constrained by the complexity of the challenge. Our research group is the first to achieve animal response-guided semiochemical lure discovery. We statistically integrated rapid field-based bioassays with scent chemical profiling and partial least squares regression to identify and test a suite of new single- and multi-compound rat lures. Field trials identified a tetrad and dyad mixture as the best performing lures, with an attraction rate of 0.61 and 0.60, respectively, compared to an attraction rate of 0.55 for the peanut butter standard. In total, 17 compound-based lures performed statistically as well as the peanut butter standard. We are currently working with an industry partner to encapsulate the lures as consumable, cost-effective pest-control products. Semiochemical lures will be particularly useful for multi-kill traps, toxic bait delivery devices, and remote monitoring devices that could operate for long periods without intervention. These devices offer substantial control program cost reductions but require long-life lures to realise their full potential.

Historically, small molecules biosynthesised by bacteria have been an excellent source for antibacterial drugs. Today, however, the rediscovery of known compounds is a significant hurdle to developing new antimicrobials. Here we use a genome mining and synthetic biology approach to discover the ambocidins: calcium‐dependent lipodepsipeptides that are active against drug‐resistant Gram‐positive pathogens. By cloning a silent biosynthetic gene cluster (the amb cluster) from Streptomyces ambofaciens ATCC 2387 and integrating this into the chromosome of Streptomyces avermitilis we induce expression of ambocidin A and B: two new Nϵ‐hydroxyarginine‐containing cyclic lipodepsipeptides active against drug‐resistant Gram‐positive pathogens. Using a panel of Streptomyces host strains, we show that the choice of heterologous host is critical for producing the biologically active compounds, and that inappropriate host choice leads to aberrant production inactive derivatives. We show that Nϵ‐hydroxyarginine is the product of a heme‐dependent oxygenase and that it enhances biological activity. Ambocidin A inhibits cell wall biosynthesis by binding to Lipid II at a different site than vancomycin. Furthermore, unlike daptomycin, ambocidin A retains potent antimicrobial activity in the presence of lung surfactant, giving it the potential to treat bacterial pneumonia. Our work expands the family of calcium‐dependent lipopeptide antibiotics with a new member exhibiting a distinct mechanism of action. [ABSTRACT FROM AUTHOR]

The potential of the diverse chemistries present in natural products (NP) for biotechnology and medicine remains untapped because NP databases are not searchable with raw data and the NP community has no way to share data other than in published papers. Although mass spectrometry (MS) techniques are well-suited to high-throughput characterization of NP, there is a pressing need for an infrastructure to enable sharing and curation of data. We present Global Natural Products Social Molecular Networking (GNPS; http://gnps.ucsd.edu), an open-access knowledge base for community-wide organization and sharing of raw, processed or identified tandem mass (MS/MS) spectrometry data. In GNPS, crowdsourced curation of freely available community-wide reference MS libraries will underpin improved annotations. Data-driven social-networking should facilitate identification of spectra and foster collaborations. We also introduce the concept of 'living data' through continuous reanalysis of deposited data.

Olfactory lures are important tools in pest-species management, being widely used to monitor and trap populations. For vertebrates like rats, lures are most commonly foods such as peanut butter. However, these are perishable and require frequent replenishment; factors that decrease control operation efficacy and increase costs. Synthetic semiochemical-based lures might address these limitations, but their identification and use for vertebrate population management remains an underexploited opportunity. We used headspace solid-phase microextraction and gas chromatography-mass spectrometry to characterise the volatile chemical profiles of 19 food products previously presented to wild, free-ranging rats and assessed for attraction. Partial least squares regression identified 10 of the 111 compounds found in two or more analysed products to be statistically significant predictors of attraction. The identity of nine of the compounds was verified using authentic samples, while one was not commercially available. Field trials used tracking tunnels to present compounds at seven different concentrations from 10,000 ppm to 0.01 ppm. Inked cards inside tracking tunnels were used to quantify visitations using species tracking marks, with the presence of rat tracks on inked cards scored to provide a tracking rate. Five compounds outperformed peanut butter while eight individual semiochemical-based lures each statistically outperformed peanut butter. Nearly half of all confirmed visits to compounds were with lures presented at 0.1 and 0.01 ppm. A trend of increasing tracking rates with decreasing lure concentration was identified for aggregated compound data. Our results suggest a number of compounds have the potential for onward development as synthetic attractants for rats. Further, the results support our integrated chemical image and response-guided approach that statistically associated behavioural responses to a range of products with the volatile compounds in those products. This approach has the potential to identify semiochemical compounds, either allelochemical or pheromone, for use as olfactory lures for managing and monitoring a range of vertebrate pest species.

Covering: January to the end of December 2022 This review covers the literature published in 2022 for marine natural products (MNPs), with 645 citations (633 for the period January to December 2022) referring to compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, the submerged parts of mangroves and other intertidal plants. The emphasis is on new compounds (1417 in 384 papers for 2022), together with the relevant biological activities, source organisms and country of origin. Pertinent reviews, biosynthetic studies, first syntheses, and syntheses that led to the revision of structures or stereochemistries, have been included. An analysis of NP structure class diversity in relation to biota source and biome is discussed. [ABSTRACT FROM AUTHOR]

The article offers information associated with protein kinase inhibitory nucleosides from the understudied phylum Bryozoa. It is noted that Adenosine triphosphate (ATP) is a critical metabolite employed by human cells to power essential life processes like cell signalling by using energy released by the cleavage of a high-energy phosphate bond.