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Pro-inflammatory cytokines, like interleukin-1 beta and interferon gamma, are known to activate signalling pathways causing pancreatic beta cell death and dysfunction, contributing to the onset of diabetes. Targeting cytokine signalling pathways offers a potential strategy to slow or even halt disease progression, reducing reliance on exogenous insulin and improving glucose regulation. This study explores the protective and proliferative effects of breitfussin C (BfC), a natural compound isolated from the Arctic marine hydrozoan Thuiaria breitfussi, on pancreatic beta cells exposed to pro-inflammatory cytokines. Using the beta cell line RIN-M5F, we assessed the protective effects of BfC through a MTS assay for cell viability, caspase 3/7 activity for apoptosis, and EdU incorporation and cell cycle distribution for proliferation. Additionally, we investigated BfC's inhibitory effects on the DYRK family of kinases using kinase activity and binding assays, western blotting, and docking simulations. Our findings reveal that BfC treatment effectively increases beta cell proliferation and counteracts cytokine-induced decrease in proliferation. The proliferative effect is associated with inhibition of DYRK kinases and a subsequent decrease in the cell cycle inhibitor p27 KIP . These results suggest that BfC mediates beta cell-protective effect by promoting proliferation through DYRK inhibition, highlighting its potential as a molecular starting point for the development of a therapeutic agent against diabetes., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

As the natural producer of acarbose, Actinoplanes sp. SE50/110 has high industrial relevance. Like most Actinobacteria, the strain carries several more putative biosynthetic gene clusters (BGCs) to produce further natural products, which are to be discovered. Applying a metabolomics-guided approach, we tentatively identified five further compounds that are produced by the strain: watasemycin, thiazostatin, isopyochelin, pulicatin, and aerugine. A comparison of the genomic context allowed the identification of the putative BGC, which is highly similar to the watasemycin biosynthetic gene cluster of Streptomyces venezuelae . In addition to the identified molecules, a thiazostatin-like compound was found. Isolation and structure elucidation with 1D and 2D NMR and HRMS were applied. The fraction containing m/z 369.0929 [M + H] + comprised two highly similar compounds identified as thiazostatin D and thiazostatin E. The compounds possessed the same phenol-thiazole-thiazole molecular scaffold as the previously reported thiazostatin and watasemycin and have anti-proliferative activity against the breast adenocarcinoma cell line MCF7 and human melanoma cell line A2058, while no activity again the non-malignant immortalized fibroblast cell line MRC-5 was observed. We further showed that the manipulation of global transcriptional regulators, with sigH ( ACSP50_0507 ) and anti-anti-σ factor coding ACSP50_0284 as an example, enabled the production manipulation of the 2-hydroxyphenylthiazoline family molecules. While the manipulation of sigH enabled the shift in the peak intensities between the five products of this pathway, ACSP50_0284 manipulation prevented their production. The production of a highly polar compound with m/z 462.1643 [M + H] + and calculated elemental composition C 19 H 27 NO 12 was activated under the ACSP50_0284 expression and is exclusively produced by the engineered strain., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Schlüter, Hansen, Isaksson, Andersen, Hansen, Kalinowski and Schneider.)

The diatom lipidome actively regulates photosynthesis and displays a high degree of plasticity in response to a light environment, either directly as structural modifications of thylakoid membranes and protein-pigment complexes, or indirectly via photoprotection mechanisms that dissipate excess light energy. This acclimation is crucial to maintaining primary production in marine systems, particularly in polar environments, due to the large temporal variations in both the intensity and wavelength distributions of downwelling solar irradiance. This study investigated the hypothesis that Arctic marine diatoms uniquely modify their lipidome, including their concentration and type of pigments, in response to wavelength-specific light quality in their environment. We postulate that Arctic-adapted diatoms can adapt to regulate their lipidome to maintain growth in response to the extreme variability in photosynthetically active radiation. This was tested by comparing the untargeted lipidomic profiles, pigmentation, specific growth rates and carbon assimilation of the Arctic diatom Porosira glacialis vs. the temperate species Coscinodiscus radiatus during exponential growth under red, blue and white light. Here, we found that the chromatic wavelength influenced lipidome remodeling and growth in each strain, with P. glacialis showing effective utilization of red light coupled with increased inclusion of primary light-harvesting pigments and polar lipid classes. These results indicate a unique photoadaptation strategy that enables Arctic diatoms like P. glacialis to capitalize on a wide chromatic growth range and demonstrates the importance of active lipid regulation in the Arctic light environment.

Bacterial symbionts of marine invertebrates are rich sources of novel, pharmaceutically relevant natural products that could become leads in combatting multidrug-resistant pathogens and treating disease. In this study, the bioactive potential of the marine invertebrate symbiont Thalassomonas actiniarum was investigated. Bioactivity screening of the strain revealed Gram-positive specific antibacterial activity as well as cytotoxic activity against a human melanoma cell line (A2058). The dereplication of the active fraction using HPLC-MS led to the isolation and structural elucidation of cholic acid and 3-oxo cholic acid. T. actiniarum is one of three type species belonging to the genus Thalassomonas . The ability to generate cholic acid was assessed for all three species using thin-layer chromatography and was confirmed by LC-MS. The re-sequencing of all three Thalassomonas type species using long-read Oxford Nanopore Technology (ONT) and Illumina data produced complete genomes, enabling the bioinformatic assessment of the ability of the strains to produce cholic acid. Although a complete biosynthetic pathway for cholic acid synthesis in this genus could not be determined based on sequence-based homology searches, the identification of putative penicillin or homoserine lactone acylases in all three species suggests a mechanism for the hydrolysis of conjugated bile acids present in the growth medium, resulting in the generation of cholic acid and 3-oxo cholic acid. With little known currently about the bioactivities of this genus, this study serves as the foundation for future investigations into their bioactive potential as well as the potential ecological role of bile acid transformation, sterol modification and quorum quenching by Thalassomonas sp. in the marine environment., Competing Interests: The authors declare no conflict of interest.

"One strain many compounds" (OSMAC) based approaches have been widely used in the search for bioactive compounds. Introducing stress factors like nutrient limitation, UV-light or cocultivation with competing organisms has successfully been used in prokaryote cultivation. It is known that diatom physiology is affected by changed cultivation conditions such as temperature, nutrient concentration and light conditions. Cocultivation, though, is less explored. Hence, we wanted to investigate whether grazing pressure can affect the metabolome of the marine diatom Porosira glacialis , and if the stress reaction could be detected as changes in bioactivity. P. glacialis cultures were mass cultivated in large volume bioreactor (6000 L), first as a monoculture and then as a coculture with live zooplankton. Extracts of the diatom biomass were screened in a selection of bioactivity assays: inhibition of biofilm formation, antibacterial and cell viability assay on human cells. Bioactivity was found in all bioassays performed. The viability assay towards normal lung fibroblasts revealed that P. glacialis had higher bioactivity when cocultivated with zooplankton than in monoculture. Cocultivation with diatoms had no noticeable effect on the activity against biofilm formation or bacterial growth. The metabolic profiles were analyzed showing the differences in diatom metabolomes between the two culture conditions. The experiment demonstrates that grazing stress affects the biochemistry of P. glacialis and thus represents a potential tool in the OSMAC toolkit.