Bioassay-Guided Fractionation Leads to the Detection of Cholic Acid Generated by the Rare Thalassomonas sp.

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

Effektiv og hensiktsmessig sikring av allmenne samfunnsinteresser i møte med markedsøknomiens krefter

Glattskurte svaberg i granitt, store områder med kystlynghei, kystfuruskog preget av vind og vær, et sjeldent og stort korallrev som er over 8.000 år gammelt. Alt dette svært sjeldne natur-ressurser vernet som Norges første marine nasjonalpark i 2009. Nasjonalparken forvaltes, og beskyttes, i stor grad av Hvaler kommunes politikere og administrasjon. Sammen med kom-munene Fredrikstad og Sarpsborg er det interkommunale selskapet Borg Havn IKS etablert for å forvalte og levere havnetjenester i dette unike kystlandskapet. Her, hvor allmenne sam-funnsinteresser møter markedsøkonomien, oppstår det gnisninger. Hvordan kan samarbeid, i de tilfeller hvor selskapsformen er et interkommunalt selskap, gjøres mer effektivt og hen-siktsmessig samtidig som politikk i større grad realiseres er i hovedsak spørsmålet denne opp-gaven i stiller. Ifølge ordføreren i Sarpsborg kommune er Borg Havn IKS et av de flotteste verktøyene eierkommunene i region Nedre Glomma har for å skape attraktivitet i sitt område. Selskapet drives kommersielt og med god økonomisk lønnsomhet. Samhandlingen mellom Hvaler kommune og Borg Havn IKS beskrives som kompleks og langt fra sømløs, men med felles målsetning om å styrke attraktiviteten til eierne. Assisterende havnedirektør i Borg Havn IKS uttaler at planprosessen til tider koster mer enn selve utbyggingen og at kompleksi-teten i samarbeidet i sum kan gi tapte muligheter for Hvaler kommune. Det har derfor vært interessant å se på hvilke faktorer som forårsaker dette lite hensiktsmessige samarbeidet, og hva som kan gjøres for å forbedre samarbeidet mellom selskapet og Hvaler kommune. Gjen-nom analyse av dagens situasjon har det vært mulig å peke på noen mulige årsakssammen-henger til dette lite hensiktsmessige samarbeidet. Det første funnet er at manglende kompe-tanse og innsikt, på begge sider av bordet, gjør samarbeidet lite effektivt. Dette fordi man ikke evner å styre prosjekt med forutsigbarhet eller være en tilstrekkelig kompetent bestiller. Dette skaper sløsing med ressurser. Det andre funnet er at det mangler hensiktsmessig eiersty-ring. Dette betyr at selskapet ikke får tilstrekkelig med føringer fra sine eiere på hva formålet med selskapet er og hvilke rammer som er satt for hvordan dette formålet skal nås. For å gjøre noe med disse funnene anbefales det å stramme opp styringen av selskapet ved å formalisere styringsverktøy slik som eierstrategi og eiermøter. I tillegg anbefales det å arbeide systematisk med kompetanseutveksling mellom kommunens administrasjon. Effekten av dette anslås til å være mer allmennyttig verdiskapning ut av få tilgjengelige ressurser.B-L

The bromotyrosine derivative Ianthelline isolated from the Arctic marine sponge Stryphnus fortis inhibits marine micro- and macrobiofouling

International audienceThe inhibition of marine biofouling by the bromotyrosine derivative ianthelline, isolated from the Arctic marine sponge Stryphnus fortis, is described. All major stages of the fouling process are investigated. The effect of ianthelline on adhesion and growth of marine bacteria and microalgae is tested to investigate its influence on the initial microfouling process comparing with the known marine antifoulant barettin as a reference. Macrofouling is studied via barnacle (Balanus improvisus) settlement assays and blue mussel (Mytilus edulis) phenoloxidase inhibition. Ianthelline is shown to inhibit both marine micro-and macrofoulers with a pronounced effect on marine bacteria (minimum inhibitory concentration (MIC) values 0.1-10 mu g/mL) and barnacle larval settlement (IC50= 3.0 mu g/mL). Moderate effects are recorded on M. edulis (IC50= 45.2 mu g/mL) and microalgae, where growth is more affected than surface adhesion. The effect of ianthelline is also investigated against human pathogenic bacteria. Ianthelline displayed low micromolar MIC values against several bacterial strains, both Gram positive and Gram negative, down to 2.5 mu g/mL. In summary, the effect of ianthelline on 20 different representative marine antifouling organisms and seven human pathogenic bacterial strains is presented

Heterocyclic cellular lipid peroxidation inhibitors inspired by the marine antioxidant barettin

Accepted manuscript version. Published version available at https://doi.org/10.1016/j.bioorg.2018.11.024. Licensed CC BY-NC-ND 4.0.The marine environment remains a rich source for the discovery and development of novel bioactive compounds. The present paper describes the design, synthesis and biological evaluation of a library of small molecule heterocyclic mimetics of the marine 2,5-diketopiperazine barettin which is a powerful natural antioxidant. By mainly focusing on the influence from the brominated indole and heterocyclic core of barettin, a library of 19 compounds was prepared. The compounds comprised a heterocyclic core, either a 2,5 diketopiperazine, an imidazolidinedione or a thioxothiazolidinone, which were mainly monosubstituted with ranging bulky substituents. The prepared compounds were screened for activity in a cellular lipid peroxidation assay using HepG2 cells. Several of the synthetic compounds showed antioxidant properties superior to the positive control barettin. Two of the prepared compounds displayed inhibitory activity similar to commercial antioxidants with significant inhibition at low µg/mL concentrations. The toxicity of the compounds was also investigated against MRC-5 lung fibroblasts and none of the included compounds displayed any toxicity at 50 µg/mL

Qualitative and Quantitative Comparison of Liquid–Liquid Phase Extraction Using Ethyl Acetate and Liquid–Solid Phase Extraction Using Poly-Benzyl-Resin for Natural Products

A key step in the process of isolating microbial natural products is the preparation of an extract from a culture. This step determines which molecules will be available for detection in the subsequent chemical and biological analysis of a biodiscovery pipeline. In the present study we wanted to document potential differences in performance between liquid–liquid extraction using ethyl acetate and liquid–solid extraction using a poly‐benzyl‐resin. For the comparison of the two extraction protocols, we spiked a culture of Flavobacterium sp. with a diverse selection of natural products of microbial and plant origin to investigate whether the methods were comparable with respect to selectivity. We also investigated the efficiency of the two extraction methods quantita‐ tively, using water spiked with a selection of natural products, and studied the quantitative effect of different pH levels of the aqueous solutions on the extraction yields of the two methods. The same compounds were extracted by the two methods, but the solid‐phase extract contained more media components compared with the liquid‐phase extract. Quantitatively, the two extraction methods varied in their recovery rates. We conclude that practical aspects could be more important when selecting one of the extraction protocols, as their efficiencies in extracting specific compounds were quite similar