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International audience; Marine sponges have a long history of farming, starting with bath sponges over 5000 years ago in the Mediterranean. Many species have since been found appropriate for distinct types of commercial assessment. Drug development relies on the isolation of sponge-derived secondary metabolites as natural compounds having a wide range of ecological functions, from deterring predation to preventing microbial infection/proliferation on the sponge body. For human society, they feature a broad array of pharmacological properties with some applications still being discovered. Their limited supply has however been faced as a major obstacle to the conduct of clinical trials. Marine aquaculture has to prove more integrated and sustainable to remain an interesting way to ensure sufficient amounts of biological substances for the early processing and production of drugs. This review presents sponge farming methods that were tested, the undergoing challenges they faced and the interest they raised on environmental and metabolic factors to explain contrasting spatiotemporal performances. Through global experiments, sometimes involving other marine organisms, technicity of sponge aquaculture has long been evolving to ensure efficient and cost-effective strategies. Further ways to make sponge farming more attractive and diversify its commercial applications are investigated, such as recent studies in collagen or chitin production for bone tissue engineering or bioremediation as an alternative to existing wastewater management. Overall, marine sponges exhibit astonishing intra and interspecific variation, which is why they should be considered with respect to the purpose of their economic valuation, their environmental context and all the symbiotic interactions they rely on.

Chemical investigation of the South-Pacific marine sponge Suberea clavata led to the isolation of eight new bromotyrosine metabolites named subereins 1–8 (2–9) along with twelve known co-isolated congeners. The detailed configuration determination of the first representative major compound of this family 11-epi-fistularin-3 (11R,17S) (1) is described. Their chemical characterization was achieved by HRMS and integrated 1D and 2D NMR (nuclear magnetic resonance) spectroscopic studies and extensive comparison with literature data. For the first time, a complete assignment of the absolute configurations for stereogenic centers C-11/17 of the known members (11R,17S) 11-epi-fistularin-3 (1) and 17-deoxyfistularin-3 (10) was determined by a combination of chemical modifications, Mosher’s technology, and ECD spectroscopy. Consequently, the absolute configurations of all our new isolated compounds 2–9 were determined by the combination of NMR, Mosher’s method, ECD comparison, and chemical modifications. Interestingly, compounds 2–7 were obtained by chemical transformation of the major compound 11-epi-fistularin-3 (1). Evaluation for acetylcholinesterase inhibition (AChE), DNA methyltransferase 1 (DNMT1) modulating activity and antifouling activities using marine bacterial strains are also presented.

International audience; Four new brominated tyrosine metabolites, aplyzanzines C-F (1-4), were isolated from the French Polynesian sponge Pseudoceratina n. sp., along with the two known 2-aminoimidazolic derivatives, purealidin A (5) and 6, previously isolated, respectively, from the sponges Psammaplysilla purpurea and Verongula sp. Their structures were assigned based on the interpretation of their NMR and HRMS data. The compounds exhibited quorum sensing inhibition (QSi) and antifouling activities against several strains of bacteria and microalgae. To our knowledge, the QSi activity of this type of bromotyrosine metabolite is described here for the first time.

WOS:000518678100003; Although the French Polynesian reefs are among the most well studied reefs of the world, sponges are still poorly known, with only 199 species or OTUs of sponges having been described from French Polynesia, 167 at an OTU level and 32 at a species level. From those 199 species, just five are calcareous sponges. As it is possible that this number is underestimated, the aim of the present work was to study the diversity of calcareous sponges from French Polynesia. Hence, different French Polynesian archipelagos were surveyed by SCUBA from 3 to 60 m of depth. Identifications were performed using morphological and molecular (ITS and C-LSU) tools. We found a total of nine species of Calcarea, comprising five different genera. Five species are new to science: Clathrina fakaravae sp. nov., Clathrina huahineae sp. nov., Ernstia variabilis sp. nov., Leucascus digitiformis sp. nov., and Leucandra tahuatae sp. nov. With the present work, the number of identified sponges from French Polynesia at a species level increased from 32 to 41. The only calcareous sponge previously known from French Polynesia that was recollected by our group was Leucetta chagosensis. Our results suggest that the Eastern Indo-Pacific Realm shows more affinity with the Central and the Western Indo-Pacific Realms Four species supported these affinities: Ascandra cf. crewsi, previously known only from Papua New Guinea, Leucascus simplex from South Australia, and Leucetta chagosensis and L. microraphis, both widespread species in the Indo-Pacific. These two Leucetta species, however, most likely represent species complexes. Once again the molecular markers ITS and C-LSU helped in the identification of calcareous sponges, showing how important is an integrative taxonomy. Although our work has increased in 250% (6 spp to 15 spp) the diversity of calcareous sponges in French Polynesia, it is most possible that this number is still underestimated.

Marine natural products isolated from the sponge Fascaplysinopsis cf reticulata, in French Polynesia, were investigated as an alternative to antibiotics to control pathogens in aquaculture. The overuse of antibiotics in aquaculture is largely considered to be an environmental pollution, because it supports the transfer of antibiotic resistance genes within the aquatic environment. One environmentally friendly alternative to antibiotics is the use of quorum sensing inhibitors (QSIs). Quorum sensing (QS) is a regulatory mechanism in bacteria which control virulence factors through the secretion of autoinducers (AIs), such as acyl-homoserine lactone (AHL) in gram-negative bacteria. Vibrio harveyi QS is controlled through three parallel pathways: HAI-1, AI-2, and CAI-1. Bioassay-guided purification of F. cf reticulata extract was conducted on two bacterial species, i.e., Tenacibaculum maritimum and V. harveyi for antibiotic and QS inhibition bioactivities. Toxicity bioassay of fractions was also evaluated on the freshwater fish Poecilia reticulata and the marine fish Acanthurus triostegus. Cyclohexanic and dichloromethane fractions of F. cf reticulata exhibited QS inhibition on V. harveyi and antibiotic bioactivities on V. harveyi and T. maritimum, respectively. Palauolide (1) and fascaplysin (2) were purified as major molecules from the cyclohexanic and dichloromethane fractions, respectively. Palauolide inhibited QS of V. harveyi through HAI-1 QS pathway at 50 μg ml–1 (26 μM), while fascaplysin affected the bacterial growth of V. harveyi (50 μg ml–1) and T. maritimum (0.25 μg). The toxicity of fascaplysin-enriched fraction (FEF) was evaluated and exhibited a toxic effect against fish at 50 μg ml–1. This study demonstrated for the first time the QSI potential of palauolide (1). Future research may assess the toxicity of both the cyclohexanic fraction of the sponge and palauolide (1) on fish, to confirm their potential as alternative to antibiotics in fish farming.

Treatment of acute myeloid leukemia (AML) patients is still hindered by resistance and relapse, resulting in an overall poor survival rate. Recently, combining specific B-cell lymphoma (Bcl)-2 inhibitors with compounds downregulating myeloid cell leukemia (Mcl)-1 has been proposed as a new effective strategy to eradicate resistant AML cells. We show here that 1(R), 6(S), 1&rsquo, (R), 6&rsquo, (S), 11(R), 17(S)-fistularin-3, a bromotyrosine compound of the fistularin family, isolated from the marine sponge Suberea clavata, synergizes with Bcl-2 inhibitor ABT-199 to efficiently kill Mcl-1/Bcl-2-positive AML cell lines, associated with Mcl-1 downregulation and endoplasmic reticulum stress induction. The absolute configuration of carbons 11 and 17 of the fistularin-3 stereoisomer was fully resolved in this study for the first time, showing that the fistularin we isolated from the marine sponge Subarea clavata is in fact the (+)-11(R), 17(S)-fistularin-3 stereoisomer keeping the known configuration 1(R), 6(S), 1&rsquo, (R), and 6&rsquo, (S) for the verongidoic acid part. Docking studies and in vitro assays confirm the potential of this family of molecules to inhibit DNA methyltransferase 1 activity.

Isolated from a New Caledonian collection of the poecilosclerid sponge Echinochalina bargibanti, arsenicin A (C3H6As4O3) was described as the first natural organic polyarsenic compound. Continuing on bioassay guided fractionation of the organic extracts of this sponge, we describe here the isolation and structural elucidation of the first sulfur-containing organic polyarsenicals ever found in nature. The novel metabolites, called arsenicin B and arsenicin C, are built on a noradamantane type framework and they further distinguish from the adamantane type framework of arsenicin A by a different heteroatom composition and by the presence of an unusual As-As bonding. Extensive 1D and 2D-NMR measurements, in combination with tandem APCI mass spectra, allowed to establish the structure of arsenicin B (C3H6As4S2) as 2. The scarcity of arsenicin C and and its intrinsic chemical instability, only allowed to collect partial spectral data which prevented the full structural definition. After extensive computational testing of several putative structures, structure 3 for arsenicin C (C3H6As4OS) was inferred by comparing experimental with DFT-calculated 1H and 13C NMR spectra. Finally, the absolute configuration of 2 and 3 were determined with a combined use of experimental and TD-DFT calculated ECD spectra and observed specific rotations. These findings pose great challenges for both the biosynthesis of these metabolites and the cycle of Arsenic in nature. Arsenicin B and arsenicin C showed strong antifungal and antibacterial activities, especially against S. aureus comparable to the antibiotic gentamycin.

WOS:000416240300004; International audience; The Indo-Pacific is the world's largest marine biogeographic region, covering the tropical and subtropical waters from the Red Sea in the Western Indian Ocean to the Easter Islands in the Pacific. It is characterized by a vast degree of biogeographic connectivity in particular in its marine realm. So far, usage of molecular tools rejected the presence of cosmopolitan or very widespread sponge species in several cases, supporting hypotheses on a higher level of endemism among marine invertebrates than previously thought. We analysed the genetic diversity of Hyrtios erectus and Stylissa massa, two alleged widespread sponge species of the Indo-Pacific, from the Red Sea and Mayotte in the West Indian Ocean to Polynesia in the Central Pacific. In the region of its type locality, the Red Sea, Hyrtios erectus is genetically distinct, and the populations from the remaining Indo-Pacific are a potentially different species and paraphyletic in respect to H. altus. Stylissa massa falls into different, but widespread genetic clades, one of them (Stylissa cf. massa), with distinct potentially hairpin-forming elements in mitochondrial intergenic regions. The results also indicate that morphologically established demosponge species in the Indo-Pacific can be widespread, but simultaneously harbour cryptic, genetically distinct lineages.

00000; International audience; Dactylospongia metachromia and Dactylospongia elegans collected from French Polynesia were studied with a particular focus on the variation of the diastereomeric ratio between ilimaquinone (4) and 5-epi-ilimaquinone (5). More than 100 samples, covering an area of 4100km(2), were studied to try to clarify this intriguing issue. Nuclear magnetic resonance appeared as the non-destructive, straightforward technique of choice for a relative quantitative study. A random distribution, unique at that point in nature, is observed and leads to biosynthetic considerations. Biological evaluation of both compounds was also performed and showed moderate discrepancies in cytotoxicity and apoptosis induction.

WOS:000414234400035; International audience; Two sporothriolide-related compounds were obtained from an extract of the fungus Hypoxylon monticulosum CLL-205, isolated from a Sphaerocladina sponge collected from the Tahiti coast. Compound 2 is a deoxy analogue of sporothric acid (4). Compound 3 is a newly reported unusual scaffold combining sporothriolide (1) and trienylfuranol A (5) moieties, through a Diels-Alderase-type reaction. Various experimental and analytical arguments supported the biocatalytic origin of compound 3. The structures of the isolated compounds were elucidated using 1D and 2D NMR, HRMS, and IR data. The structure and the absolute configuration of 3 were unambiguously confirmed by a single-crystal X-ray diffraction analysis.

International audience; Highly biologically active marine sesquiterpene ilimaquinone was selected for chemical modifications. Its biotransformation was investigated using a combinatorial approach as an original way to screen different strains of microorganisms. Mucor circinelloides ATCC 8541 was able to structurally modify ilimaquinone into three different compounds. A stereospecific epoxidation was observed and compared to chemical epoxidation. A hydroxylation of the decalin ring was also observed as well as an unexpected substitution on the quinone ring by ethanolamine. Compounds were evaluated against several cell lines.

The debromokeramadine ( 2a ), which was isolated from the Pacific sponge Agelas cf. mauritiana , is described in this manuscript. We also report the synthesis of the debromokeramadine ( 2a ) and its known brominated analog, keramadine ( 1 ), based on the regioselective oxidative addition of a guanidine derivative on N -acylpyrrole dihydropyridines. This flexible approach was applied to the preparation of three debromo-analogs 2b – d by varying the substitution of the guanidine bis-nucleophile. The reaction is a great progress for the regio- and stereoselective synthesis of debromokeramadine ( 2a ) analogs and interesting library of pyrrole-2-aminoimidazole allowing biological activity studies.

International audience; Symbioses with the dinoflagellate Symbiodinium are widespread among marine invertebrates and protists, especially in nutritionally demanding habitats, such as tropical coral reefs, where they play a major role in ecosystem survival. Moreover, apart from corals and sea anemones, many of the Symbiodinium species and clades involved in these partnerships remain to be characterized. This study provides new insights into nudibranch and sponge associations with Symbiodinium by sequencing regions of the Symbiodinium 28S rDNA and the host mitochondrial COI oxidase. Specimens were sampled between 2011 and 2013 from locations around the islands of Moorea and Tahiti, French Polynesia. Our results revealed that some of the sponges and nudibranchs harbored typical Symbiodinium from clade B or C while others harbored new, undescribed Symbiodinium-like dinoflagellates. A detailed analysis of the different life stages of the nudibranch Phestilla lugubris and of its specific coral prey, Porites rus, suggests a prey-predator horizontal transfer of the symbiont and its vertical inheritance from the parent to the eggs.; Les symbioses à zooxanthelles, dinoflagellés du genre Symbiodinium, sont largement répandues chez les invertébrés marins et les protozoaires, notamment dans les eaux oligotrophes, où ils jouent un rôle important dans la survie des récifs coralliens. De plus, excepté chez les coraux et les anémones, les différentes espèces et clades de Symbiodinium impliqués dans ces associations restent à être caractérisés. Notre étude, grâce à l’utilisation des marqueurs génétiques 28S ADNr des Symbiodinium et la sous-unité 1 de la cytochrome oxydase mitochondriale (COI) de l’hôte, procure de nouvelles données quant aux associations des éponges et des nudibranches avec les Symbiodinium. L’échantillonnage a eu lieu autour de Moorea et de Tahiti (Polynésie française), entre 2011 et 2013. Nos résultats révèlent que certaines espèces d’éponges et de nudibranches possèdent les clades B et C communément retrouvés, chez les coraux notamment, alors que d’autres présentent de nouveaux dinoflagellés « Symbiodinium-like ». Une analyses détaillée des Symbiodinium à différents stades du cycle de vie du nudibranche corallivore Phestilla lugubris et de son corail hôte Porites rus suggèrent l’existence d’un transfert horizontal de Symbiodinium proie–prédateur et un transfert vertical du parent P. lugubris à ses œufs.

Seven 2,5-diketopiperazines (DKPs) were isolated from the Fijian marine sponge Acanthella cavernosa. NMR and circular dichroism (CD) comparison with synthetic L-L DKPs allowed us to determine unambiguously the L-L absolute configuration of the natural DKPs. This work initiated the setting up of an optical properties database of natural DKPs, including specific rotation and CD. 2,5-Diketopiperazines (DKPs) are cyclic secondary metabolites directly resulted from the primary peptidic metabolites. They have been detected in beverages, foods and microorganisms. As the smallest cyclic peptides, DKPs provide interesting biological properties such as organoleptical, antitumoral, antifungal, antibacterial, antifouling and antiviral activities. 2 Many natural metabolites including alkaloids are biosynthetically derived from diketopiperazines by oxidation and rearrangement reactions. They represent an interesting tool for medicinal chemistry since their heterocyclic cores provide a good template for further chemical and stereochemical modification. Proline (Pro) and arginine (Arg) units are usually found in biologically active DKPs. Despite the increasing interest of DKPs, their stereochemical information was not well documented. DKP derivatives have attracted significant attention because of their potential rule as important class of multifunctional biomolecules. Their putative roles as signaling molecules in the chemical ecology context is more and more considered. Thus, determination of absolute configuration of cyclic dipeptides is of significant importance. As a part of our on-going research on bioactive natural compounds from Pacific Axinellidae marine sponges, a scrutinized study of secondary metabolites of a Fijian sample of the marine sponge Acanthella HETEROCYCLES, Vol. 90, No. 2, 2015 1351

International audience

International audience; Four samples of Suberea ianthelliformis were investigated and furnished five new and 13 known brominated tyrosine-derived compounds. Two of the new compounds were identified as araplysillin N20-formamide and its N-oxide derivative. Three other new compounds, araplysillins IV, V, and VI, were isolated and identified as analogs of araplysillin II. Most of these compounds exhibit moderate inhibitory activities against chloroquine-resistant and -sensitive strains of Plasmodium falciparum, and were investigated for their PFTase inhibitory properties. The chemical content of the investigated sponges is correlated with their molecular phylogeny.

International audience; Pipestelides A-C (2-4) are three new NRPS-PKS hybrid macrolides containing uncommon moieties, isolated from the Pacific marine sponge Pipestela candelabra. Their structures were elucidated on the basis of spectroscopic data. These cyclodepsipeptides appear to be biosynthetically related to jaspamide (aka jasplakinolide) (1) by chemical modification of the building blocks of the polyketide or peptide chains. Pipestelides A-C (2-4) contain a bromotyrosine [3-amino-3-(bromo-4-hydroxyphenyl)propanoic acid] unit, a polypropionate with a Z double bond, and a 2-hydroxyquinolinone, respectively. Revised chemical shift assignments are provided for the co-isolated known jasplakinolide C(a) (5). In addition, compounds 2 and 3 exhibited cytotoxic activities in the micromolar range.

International audience

Two unprecedented cyclic peptides, solomonamides A and B, were isolated from the marine sponge Theonella swinhoei. The structures were elucidated on the basis of comprehensive 1D and 2D NMR analysis and high-resolution mass spectrometry. A combined approach, involving Marfey's method, QM J based analysis, and DFT J/(13)C calculations, was used for establishing the absolute configuration of the entire molecule. Solomonamide A showed in vivo anti-inflammatory activity.

International audience; Indole derivatives including bromoindoles have been isolated from the South Pacific marine sponges Rhopaloeides odorabile and Hyrtios sp. Their structures were established through analysis of mass spectra and 1D and 2D NMR spectroscopic data. Their potential inhibitory phospholipase A₂ (PLA₂), antioxidant and cytotoxic activities were evaluated. The new derivative 5,6-dibromo-L-hypaphorine (9) isolated from Hyrtios sp. revealed a weak bee venom PLA₂ inhibition (IC₅₀ 0.2 mM) and a significant antioxidant activity with an Oxygen Radical Absorbance Capacity (ORAC) value of 0.22. The sesquiterpene aureol (4), also isolated from Hyrtios sp., showed the most potent antioxidant activity with an ORAC value of 0.29.

Theirintriguingdimeric polycyclic ring systems that were isolated during thelast years revealed their elaborate structures and moleculardiversity which arise from a variety of modes of dimerizationand polycyclization. Structurally, it is assumed that thesemetabolites arise from the crucial intermediates clathrodin

International audience

International audience; Four new dimeric pyrrole-2-aminoimidazole alkaloids have been isolated from the Pacific marine sponges Agelas cf. mauritiana and Phakellia sp. They include the unusual C2 symmetrical benzosceptrins A (4) and B (5), which each possess a unique benzocyclobutane skeleton and nagelamides S (6) and T (7). Their structures and relative configuration were elucidated from spectroscopic data. Plausible biogenetic paths for these compounds are also proposed in this paper.

International audience; Nine new cyclodepsipeptides, homophymines B-E (2-5) and A1-E1 (1a-5a), were isolated from the polar extracts of the sponge Homophymia sp. The new structures, featuring new polyketide-derived end groups, were determined by interpretation of NMR and MS data. The configurations of the new end groups was secured by the application of J-based configurational analysis. Homophymines displayed very potent antiproliferative activity (IC(50) in the nM range) against a panel of human cancer cell lines.

International audience; Three new pregnanes, ptilosteroid A (1), ptilosteroid B (2), and ptilosteroid C (3), and two new pregnane glycosides, ptilosaponoside A (4) and ptilosaponoside B (5), were isolated from the marine sponge Ptilocaulis spiculifer collected in the Solomon Islands. The structures were determined by spectroscopic methods. Biological tests of these compounds showed that they are not cytotoxic against KB cells.

International audience

International audience; New debromopyrrole-2-aminoimidazolones, debromodispacamide B (1) and debromodispacamide D (2) were isolated from the sponge Agelas mauritiana, collected in the Solomon Islands. A biomimetic one-step reaction from pseudopeptides 5 and 13 in presence of air oxygen and guanidine gave the chiral form of the natural product stereoselectively.

Our team is one of the partners of the international project PoMaRe ("Benthic Invertebrates of Polynesia, Martinique and Reunion"). We worked directly with Dr. Cécile Debitus from the IRD in French Polynesia, her team was in charge of collecting samples of marine sponges in different atolls of the Pacific.In the laboratory, we focused particularly on two abundant species in Polynesia: Dactylospongia metachromia and Dactylospongia elegans. Our job was to isolate their major metabolites: the ilimaquinones and perform various studies around these two epimeric sesquiterpene quinones.The work was organized as follows:- Extraction of ilimaquinones: ilimaquinones were isolated from the sponge Dactylospongia metachromia with a yield > 3%. A study of the variation of their respective percentage in relation with the geography of collection was undertaken, involving more than one hundred samples. This is the first study of this scale to be achieved. The sponge D. elegans was also studied, our results revealed the presence of ilimaquinone but also a nearby structure: isospongiaquinone.- Structural modifications of ilimaquinones:* Chemical modifications: structural changes were studied on ilimaquinones to delimit their reactivity: various analogues have been obtained. Among others, natural substances isospongiaquinone, 5-epi-isospongiaquinone and neomamanuthaquinone have been obtained. In these studies, a new reaction was discovered modifying the quinone surprisingly under oxidizing conditions.* Enzymatic modifications: micro-organisms were used to carry out biotransformations on the skeleton of ilimaquinone, three compounds were obtained. These changes have affected both the decalin and the quinone of our substrate. An original reaction has also been observed for the first time.-Molecular modeling and electrochemistry: a molecular modeling study has allowed us to calculate the energy of formation of ilimaquinones based on biosynthesis assumptions that we can now better understand. Finally an electrochemistry study evaluated the redox properties of these natural molecules with high potential in terms of biological activity.; Notre équipe est l’un des partenaires du projet international PoMaRé (« Invertébrésbenthiques de Polynésie, Martinique et de la Réunion »). Nous travaillons encollaboration directe avec le Dr Cécile Debitus de l’IRD en Polynésie française, sonéquipe étant notamment en charge de collecter des échantillons d’éponges marinesdans différents atolls du Pacifique.Au laboratoire, nous nous sommes intéressés particulièrement à deux espècesabondantes en Polynésie : Dactylospongia metachromia et Dactylospongia elegans.Notre travail a consisté à isoler leurs métabolites spécialisés majoritaires : lesilimaquinones, puis à réaliser diverses études autour de ces deux sesquiterpènesquinoniques épimériques. Le travail s’est organisé de la façon suivante :- Extraction des ilimaquinones : les ilimaquinones ont été isolées de l’éponge Dactylospongia metachromia avec un rendement > 3 %. Une étude de la variation de leur pourcentage respectif par rapport à la géographie de collecte de l’éponge a été entreprise. Impliquant plus d’une centaine d’échantillons, c’est la première fois qu’une étude d’une telle ampleur est réalisée. L’éponge D. elegans a également été étudiée, nos études ont révélé la présence de l’ilimaquinone mais aussi d’une structure proche : l’isospongiaquinone.- Modifications structurales autour des ilimaquinones : Par voie chimique : des modifications ont été étudiées sur les ilimaquinones afin de cerner leur réactivité, divers analogues ont ainsi été obtenus. Entre autres, les substances naturelles isospongiaquinone, 5-epi-isospongiaquinone et néomamanuthaquinone ont pu être hémisynthétisées. Lors de ces études, une nouvelle réaction a été découverte modifiant la quinone de façon surprenante dans des conditions oxydantes. Par voie enzymatique : des micro-organismes ont été utilisés pour réaliser des biotransformations sur le squelette de l’ilimaquinone, trois composés ont été obtenus. Ces modifications ont touché à la fois la décaline et la quinone de notre substrat. Une réaction de fonctionnalisation originale a d’ailleurs pu être observée pour la première fois.- Modélisation moléculaire et électrochimie : une étude de modélisation moléculaire nous a permis de calculer l’énergie de formation des ilimaquinones en nous basant sur les hypothèses de biosynthèse que nous pouvons maintenant mieux appréhender. Finalement une étude d’électrochimie nous a permis d’évaluer les propriétés oxydo-réductrices de ces molécules naturelles à fortes potentialités en termes d’activités biologiques.

Our team is one of the partners of the international project PoMaRe ("Benthic Invertebrates of Polynesia, Martinique and Reunion"). We worked directly with Dr. Cécile Debitus from the IRD in French Polynesia, her team was in charge of collecting samples of marine sponges in different atolls of the Pacific.In the laboratory, we focused particularly on two abundant species in Polynesia: Dactylospongia metachromia and Dactylospongia elegans. Our job was to isolate their major metabolites: the ilimaquinones and perform various studies around these two epimeric sesquiterpene quinones.The work was organized as follows:- Extraction of ilimaquinones: ilimaquinones were isolated from the sponge Dactylospongia metachromia with a yield > 3%. A study of the variation of their respective percentage in relation with the geography of collection was undertaken, involving more than one hundred samples. This is the first study of this scale to be achieved. The sponge D. elegans was also studied, our results revealed the presence of ilimaquinone but also a nearby structure: isospongiaquinone.- Structural modifications of ilimaquinones:* Chemical modifications: structural changes were studied on ilimaquinones to delimit their reactivity: various analogues have been obtained. Among others, natural substances isospongiaquinone, 5-epi-isospongiaquinone and neomamanuthaquinone have been obtained. In these studies, a new reaction was discovered modifying the quinone surprisingly under oxidizing conditions.* Enzymatic modifications: micro-organisms were used to carry out biotransformations on the skeleton of ilimaquinone, three compounds were obtained. These changes have affected both the decalin and the quinone of our substrate. An original reaction has also been observed for the first time.-Molecular modeling and electrochemistry: a molecular modeling study has allowed us to calculate the energy of formation of ilimaquinones based on biosynthesis assumptions that we can now better understand. Finally an electrochemistry study evaluated the redox properties of these natural molecules with high potential in terms of biological activity.; Notre équipe est l’un des partenaires du projet international PoMaRé (« Invertébrésbenthiques de Polynésie, Martinique et de la Réunion »). Nous travaillons encollaboration directe avec le Dr Cécile Debitus de l’IRD en Polynésie française, sonéquipe étant notamment en charge de collecter des échantillons d’éponges marinesdans différents atolls du Pacifique.Au laboratoire, nous nous sommes intéressés particulièrement à deux espècesabondantes en Polynésie : Dactylospongia metachromia et Dactylospongia elegans.Notre travail a consisté à isoler leurs métabolites spécialisés majoritaires : lesilimaquinones, puis à réaliser diverses études autour de ces deux sesquiterpènesquinoniques épimériques. Le travail s’est organisé de la façon suivante :- Extraction des ilimaquinones : les ilimaquinones ont été isolées de l’éponge Dactylospongia metachromia avec un rendement > 3 %. Une étude de la variation de leur pourcentage respectif par rapport à la géographie de collecte de l’éponge a été entreprise. Impliquant plus d’une centaine d’échantillons, c’est la première fois qu’une étude d’une telle ampleur est réalisée. L’éponge D. elegans a également été étudiée, nos études ont révélé la présence de l’ilimaquinone mais aussi d’une structure proche : l’isospongiaquinone.- Modifications structurales autour des ilimaquinones : Par voie chimique : des modifications ont été étudiées sur les ilimaquinones afin de cerner leur réactivité, divers analogues ont ainsi été obtenus. Entre autres, les substances naturelles isospongiaquinone, 5-epi-isospongiaquinone et néomamanuthaquinone ont pu être hémisynthétisées. Lors de ces études, une nouvelle réaction a été découverte modifiant la quinone de façon surprenante dans des conditions oxydantes. Par voie enzymatique : des micro-organismes ont été utilisés pour réaliser des biotransformations sur le squelette de l’ilimaquinone, trois composés ont été obtenus. Ces modifications ont touché à la fois la décaline et la quinone de notre substrat. Une réaction de fonctionnalisation originale a d’ailleurs pu être observée pour la première fois.- Modélisation moléculaire et électrochimie : une étude de modélisation moléculaire nous a permis de calculer l’énergie de formation des ilimaquinones en nous basant sur les hypothèses de biosynthèse que nous pouvons maintenant mieux appréhender. Finalement une étude d’électrochimie nous a permis d’évaluer les propriétés oxydo-réductrices de ces molécules naturelles à fortes potentialités en termes d’activités biologiques.

The bacterial resistance induced by the massive use of antibiotics in aquaculture, leads to the search for new treatment methods, anti-virulent and non-toxic treatments. Different strategies are studied among which the inhibition of a system of regulation: the quorum sensing. Vibrio harveyi is a pathogenic bacterium in aquaculture that regulates its bioluminescence and the production of virulence proteins through quorum sensing. The study of sponges Leucetta chagosensis, Dysidea sp. 2669 and Cacospongia sp. 2110 collected in French Polynesia, allowed the isolation of eight secondary metabolites including four new ones: isonaamine D, bis-isonaamidine A-Zn, leucettamine D and tuamotuolol. Their effects and their modes of action were evaluated on two phenotypes controlled by quorum sensing in V. harveyi: bioluminescence and production of metalloproteases. Three molecules have thus shown an inhibitory activity of the quorum sensing of V. harveyi: isonaamine D, isonaamidine A and ilimaquinone., La résistance bactérienne induite par l’utilisation massive d’antibiotiques en aquaculture, conduit à la recherche de nouveaux modes de traitement, des traitements anti-virulents et non toxiques. Différentes stratégies sont étudiées parmi lesquelles l’inhibition d’un système de régulation : le quorum sensing. Vibrio harveyi est une bactérie pathogène en aquaculture qui régule sa bioluminescence et la production de protéines de virulence par l’intermédiaire du quorum sensing. L’étude des éponges Leucetta chagosensis, Dysidea sp. 2669 et Cacospongia sp. 2110 collectées en Polynésie française, a permis l’isolement de huit métabolites secondaires dont quatre nouveaux : l’isonaamine D, le bis-isonaamidine A-Zn, la leucettamine D et le tuamotuolol. Leurs effets et leurs modes d’action ont été évalués sur deux phénotypes contrôlés par le quorum sensing chez V. harveyi: la bioluminescence et la production de métalloprotéases. Trois molécules ont ainsi montré une activité inhibitrice du quorum sensing de V. harveyi : l’isonaamine D, l’isonaamidine A et l’ilimaquinone.