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The aim of this research is to propose simple and scalable processes to obtain bioactive peptides extensively hydrolyzed starting from a tuna mixed biomass. The upcycling of this powdered biomass is challenging since it comes from the unsorted industrial side streams of the tuna canning process (cooked residues from fillet trimming) after a patented mild dehydration useful for preventing its degradation until its exploitation. Two different protocols were proposed, with and without the inclusion of an exogenous enzyme (Enzymatic-Assisted Extraction, EAE), with no relevant differences in yields (24% vs. 22%) and a comparable amino acid composition. Nevertheless, the former protocol (with EAE) provided peptides with an average molecular weight of 1.3 kDa, and the second one (without EAE) provided peptides with an average molecular weight of 2.2 kDa. The two corresponding types of tuna protein hydrolysates (Enzymatic Hydrolysates (EH) and Non-Enzymatic Hydrolysates (NEH)) were characterized by proximate compositions, pH, color profile, amino acid analysis, FTIR spectra, and molecular weight distribution. In addition, several biological analyses were performed to assess their potential use as nutraceutical supplements: special attention has been paid to antioxidant activity using three different methods to quantify it. EH showed the most promising antioxidant activity which could be exploited also in other fields (e.g., biomaterials, cosmetics). [ABSTRACT FROM AUTHOR]

Farmed lumpfish (Cyclopterus lumpus) are used as cleaner fish in Norwegian aquaculture. However, once the fish reaches sexual maturity, it becomes less effective in combating lice and is often wasted or turned into silage. This raises ethical, economic, and sustainability concerns regarding whether the use is sustainable without increasing its standard of living and further use of the fish to higher value products. To improve the utilization of lumpfish, a study was conducted to investigate the differences in extraction efficiency by comparing product yield, protein content, and peptide size distribution after enzymatic hydrolysis of lumpfish using several commercial proteases (Corolase 8,000, Corolase 7,089, Endocut 01 L, Flavourzyme, and Food Pro PNL), and different pretreatment methods (pulsed electric field and high-pressure processing). The choice of enzyme did not affect the amino acid contents of the different hydrolysates. Furthermore, varying enzyme concentrations had a minor impact on the final product's protein content. As anticipated, increased enzyme concentrations decreased the hydrolysates' average molecular weight. The study found that biomass treated either chemically (NaOH and butanol) or mechanically with a pulsed electric field before enzymatic hydrolysis resulted in higher protein content and relatively higher amounts of collagen peptides. Initial bioactivity testing indicated that the hydrolysates had no toxic effects on hepatocellular carcinoma and non-malignant lung fibroblast cells. Previous studies have shown that farmed lumpfish contains all the essential amino acids and has high levels of EPA, DHA, B12, and D3 vitamins. The contents of environmental pollutants and heavy metals were also below the EU maximum levels. This study's knowledge and results open for the potential use of lumpfish peptides and gelatin for, e.g., dietary supplements, feed, and biodegradable packaging. [ABSTRACT FROM AUTHOR]

The enzymatic extraction of proteins from fish biomasses is being widely investigated. However, little or almost no research has paid attention to the exploitation of unsorted fishery biomasses. This work is part of a larger study, Part I of which has already been published, and focuses on an extensive characterization of two collagenous samples, namely gelatin (G) and hydrolyzed gelatin peptides (HGPs), extracted from a dehydrated fish biomass coming from unsorted canned yellowfin tuna side streams. The results indicate crude protein fractions of 90–93%, pH values between 3 and 5, white–yellow colors, collagen-like FTIR spectra, and 17% in terms of total amino acid content. Viscosity and the study of dynamic viscous–elastic behavior were analyzed. Thermo-gravimetric analysis was performed to assess the residual ashes. Both samples were investigated to determine their molecular weight distribution via size-exclusion chromatography, with a higher total average molecular weight for G compared to HGPs, with values of 17,265.5 Da and 2637.5 Da, respectively. G demonstrated technological properties similar to analogous marine gelatins. HGPs demonstrated antioxidant activity as per FRAP assay. All the results open up new perspectives for the potential use of these substances in biodegradable packaging, dietary supplements, and skin care cosmetics. [ABSTRACT FROM AUTHOR]

Isolation of bioactive products from the marine environment is considered a very promising approach to identify new compounds that can be used for further drug development. In this work we have isolated three new compounds from the purpuroine family by mass-guided preparative HPLC; purpuroine K-M. These compounds where screened for antibacterial- and antifungal activity, antibiofilm formation and anti-cell proliferation activity. Additionally, apoptosis-, cell cycle-, kinase binding- and docking studies were performed to evaluate the mechanism-of-action. None of the compounds showed activity in antibacterial-, antibiofilm- or antifungal assays. However, one of the isolated compounds, purpuroine K, showed activity against two cell lines, MV-4-11 and MOLM-13, two AML cell lines both carrying the FTL3-ITD mutation. In MV-4-11 cells, purpuroine K was found to increase apoptosis and arrest cells cycle in G1/G0, which is a common feature of FLT3 inhibitors. Interactions between purpuroine K and the FLT3 wild type or FLT3 ITD mutant proteins could however not be elucidated in our kinase binding and docking studies. In conclusion, we have isolated three novel molecules, purpuroine K-M, one of which (purpuroine K) shows a potent activity against FLT3-ITD mutated AML cell lines, however, the molecular target(s) of purpuroine K still need to be further investigated. [ABSTRACT FROM AUTHOR]

Treatment options for infections caused by antimicrobial-resistant bacteria are rendered ineffective, and drug alternatives are needed—either from new chemical classes or drugs with new modes of action. Historically, natural products have been important contributors to drug discovery. In a recent study, the dimeric naphthopyrone lulworthinone produced by an obligate marine fungus in the family Lulworthiaceae was discovered. The observed potent antibacterial activity against Gram-positive bacteria, including several clinical methicillin-resistant Staphylococcus aureus (MRSA) isolates, prompted this follow-up mode of action investigation. This paper aimed to characterize the antibacterial mode of action (MOA) of lulworthinone by combining in vitro assays, NMR experiments and microscopy. The results point to a MOA targeting the bacterial membrane, leading to improper cell division. Treatment with lulworthinone induced an upregulation of genes responding to cell envelope stress in Bacillus subtilis. Analysis of the membrane integrity and membrane potential indicated that lulworthinone targets the bacterial membrane without destroying it. This was supported by NMR experiments using artificial lipid bilayers. Fluorescence microscopy revealed that lulworthinone affects cell morphology and impedes the localization of the cell division protein FtsZ. Surface plasmon resonance and dynamic light scattering assays showed that this activity is linked with the compound's ability to form colloidal aggregates. Antibacterial agents acting at cell membranes are of special interest, as the development of bacterial resistance to such compounds is deemed more difficult to occur. [ABSTRACT FROM AUTHOR]

The emergence of drug-resistant bacteria is increasing rapidly in all parts of the world, and the need for new antibiotics is urgent. In our continuous search for new antimicrobial molecules from under-investigated Arctic marine microorganisms, a marine fungus belonging to the family Lulworthiaceae (Lulworthiales, Sordariomycetes, and Ascomycota) was studied. The fungus was isolated from driftwood, cultivated in liquid medium, and studied for its potential for producing antibacterial compounds. Through bioactivity-guided isolation, a novel sulfated biarylic naphtho-α-pyrone dimer was isolated, and its structure was elucidated by spectroscopic methods, including 1D and 2D NMR and HRMS. The compound, named lulworthinone (1), showed antibacterial activity against reference strains of Staphylococcus aureus and Streptococcus agalactiae , as well as several clinical MRSA isolates with MICs in the 1.56–6.25 μg/ml range. The compound also had antiproliferative activity against human melanoma, hepatocellular carcinoma, and non-malignant lung fibroblast cell lines, with IC50 values of 15.5, 27, and 32 μg/ml, respectively. Inhibition of bacterial biofilm formation was observed, but no eradication of established biofilm could be detected. No antifungal activity was observed against Candida albicans. During the isolation of 1 , the compound was observed to convert into a structural isomer, 2 , under acidic conditions. As 1 and 2 have high structural similarity, NMR data acquired for 2 were used to aid in the structure elucidation of 1. To the best of our knowledge, lulworthinone (1) represents the first new bioactive secondary metabolite isolated from the marine fungal order Lulworthiales. [ABSTRACT FROM AUTHOR]

Natural products and their derivatives have served as powerful therapeutics against pathogenic microorganisms and are the mainstay of our currently available treatment options to combat infections. As part of our ongoing search for antimicrobial natural products from marine organisms, one fraction prepared from the Arctic marine bryozoan Securiflustra securifrons was found to be active against the human pathogenic bacterium Streptococcus agalactiae (gr. B). Chemical investigation of the fraction revealed that it contained several variants of the highly modified secondary metabolites known as securamines. The securamines are alkaloids sharing a common isoprene-histamine-tryptamine backbone. In this study, we describe the antimicrobial activities of securamine C, E, and H - J (4, 5, and 1-3) and the attempt to deconvolute the mode of action of 1. [ABSTRACT FROM AUTHOR]

As part of our search for bioactive metabolites from understudied marine microorganisms, the new chlorinated metabolite chlovalicin B (1) was isolated from liquid cultures of the marine basidiomycete Digitatispora marina, which was collected and isolated from driftwood found at Vannøya, Norway. The structure of the novel compound was elucidated by spectroscopic methods including 1D and 2D NMR and analysis of HRMS data, revealing that 1 shares its molecular scaffold with a previously isolated compound, chlovalicin. This represents the first compound isolated from the Digitatispora genus, and the first reported fumagillin/ovalicin-like compound isolated from Basidiomycota. Compound 1 was evaluated for antibacterial activities against a panel of five bacteria, its ability to inhibit bacterial biofilm formation, for antifungal activity against Candida albicans, and for cytotoxic activities against malignant and non-malignant human cell lines. Compound 1 displayed weak cytotoxic activity against the human melanoma cell line A2058 (~50% survival at 50 µM). No activity was detected against biofilm formation or C. albicans at 50 µM, or against bacterial growth at 100 µM nor against the production of cytokines by the human acute monocytic leukemia cell line THP-1 at 50 µM. [ABSTRACT FROM AUTHOR]

The Lacinutrix genus was discovered in 2005 and includes 12 Gram-negative bacterial species. To the best of our knowledge, the secondary metabolite production potential of this genus has not been explored before, and examination of Lacinutrix species may reveal novel chemistry. As part of a screening project of Arctic marine bacteria, the Lacinutrix sp. strain M09B143 was cultivated, extracted, fractionated and tested for antibacterial and cytotoxic activities. One fraction had antibacterial activity and was subjected to mass spectrometry analysis, which revealed two compounds with elemental composition that did not match any known compounds in databases. This resulted in the identification and isolation of two novel isobranched lyso-ornithine lipids, whose structures were elucidated by mass spectrometry and NMR spectroscopy. Lyso-ornithine lipids consist of a 3-hydroxy fatty acid linked to the alpha amino group of an ornithine amino acid through an amide bond. The fatty acid chains were determined to be iso-C15:0 (1) and iso-C16:0 (2). Compound 1 was active against the Gram-positive S. agalactiae, while 2 showed cytotoxic activity against A2058 human melanoma cells. [ABSTRACT FROM AUTHOR]

Siderophores are compounds with high affinity for ferric iron. Bacteria produce these compounds to acquire iron in iron-limiting conditions. Iron is one of the most abundant metals on earth, and its presence is necessary for many vital life processes. Bacteria from the genus Serratia contribute to the iron respiration in their environments, and previously several siderophores have been isolated from this genus. As part of our ongoing search for medicinally relevant compounds produced by marine microbes, a co-culture of a Shewanella sp. isolate and a Serratia sp. isolate, grown in iron-limited conditions, was investigated, and the rare siderophore serratiochelin A (1) was isolated with high yields. Compound 1 has previously been isolated exclusively from Serratia sp., and to our knowledge, there is no bioactivity data available for this siderophore to date. During the isolation process, we observed the degradation product serratiochelin C (2) after exposure to formic acid. Both 1 and 2 were verified by 1-D and 2-D NMR and high-resolution MS/MS. Here, we present the isolation of 1 from an iron-depleted co-culture of Shewanella sp. and Serratia sp., its proposed mechanism of degradation into 2, and the chemical and biological characterization of both compounds. The effects of 1 and 2 on eukaryotic and prokaryotic cells were evaluated, as well as their effect on biofilm formation by Staphylococcus epidermidis. While 2 did not show bioactivity in the given assays, 1 inhibited the growth of the eukaryotic cells and Staphylococcus aureus. [ABSTRACT FROM AUTHOR]