An integrative approach to decipher the chemical antagonism between the competing endophytes paraconiothyrium variabile and Bacillus subtilis

An integrative approach combining traditional natural products chemistry, molecular networking, and mass spectrometry imaging has been undertaken to decipher the molecular dialogue between the fungus Paraconiothyrium variabile and the bacterium Bacillus subtilis, which were isolated as endophytes from the conifer Cephalotaxus harringtonia and are characterized by a strong and mutual antibiosis. From this study, we highlight that bacterial surfactins and a fungal tetronic acid are involved in such competition and that the fungus is able to hydrolyze surfactins to fight against the bacterial partner

Photodegradation of the Mycobacterium ulcerans Toxin, Mycolactones: Considerations for Handling and Storage

Background: Mycolactones are toxins secreted by M. ulcerans, the etiological agent of Buruli ulcer. These toxins, which are the main virulence factors of the bacilli, are responsible for skin lesions. Considering their specificity for M. ulcerans and their presence in skin lesions even at early stages, mycolactones are promising candidates for the development of a diagnostic tool for M. ulcerans infection. Stability of purified mycolactones towards light and heat has not yet been investigated, despite the importance of such parameters in the selection of strategies for a diagnosis tool development. In this context, the effects of UV, light and temperature on mycolactone stability and biological activity were studied. Methodology/Principal Findings: To investigate the effect of these physical parameters, mycolactones were exposed to different wavelengths in several solvents and temperatures. Structural changes and biological activity were monitored. Whilst high temperature had no effect on mycolactones, UV irradiation (UV-A, UV-B and UV-C) and sunlight exposure caused a considerable degradation, as revealed by LC-MS and NMR analysis, correlated with a loss of biological activity. Moreover, effect of UVs on mycolactone caused a photodegradation rather than a phototransformation due to the identification of degradation product. Conclusion/Significance: This study demonstrates the high sensitivity of mycolactones to UVs as such it defines instruction

Recent progress in marine mycological research in different countries, and prospects for future developments worldwide

Early research on marine fungi was mostly descriptive, with an emphasis on their diversity and taxonomy, especially of those collected at rocky shores on seaweeds and driftwood. Subsequently, further substrata (e.g. salt marsh grasses, marine animals, seagrasses, sea foam, seawater, sediment) and habitats (coral reefs, deep-sea, hydrothermal vents, mangroves, sandy beaches, salt marshes) were explored for marine fungi. In parallel, research areas have broadened from micro-morphology to ultrastructure, ecophysiology, molecular phylogenetics, biogeography, biodeterioration, biodegradation, bioprospecting, genomics, proteomics, transcriptomics and metabolomics. Although marine fungi only constitute a small fraction of the global mycota, new species of marine fungi continue to be described from new hosts/substrata of unexplored locations/habitats, and novel bioactive metabolites have been discovered in the last two decades, warranting a greater collaborative research effort. Marine fungi of Africa, the Americas and Australasia are under-explored, while marine Chytridiomycota and allied taxa, fungi associated with marine animals, the functional roles of fungi in the sea, and the impacts of climate change on marine fungi are some of the topics needing more attention. In this article, currently active marine mycologists from different countries have written on the history and current state of marine fungal research in individual countries highlighting their strength in the subject, and this represents a first step towards a collaborative inter- and transdisciplinary research strategy

Synthèses et évaluations biologiques d'analogues de substances naturelles (pyranodibenzofuranes à potentialité antituberculeuse et benzo[c]phénanthrolines cytotoxiques)

Les substances naturelles représentent une source importante de molécules d'intérêt thérapeutique. Leur grande diversité peut être exploitée en tant que telle mais ils peuvent aussi fournir de nouvelles têtes de série.C''st pourquoi notre travail a porté sur la synthèse de composés de séries pyranodibenzofurane et benzo[c]phénanthroline analogues de composés naturels. La première partie porte sur la synthèse de pyranodibenzofuranes comportant deux motifs d'origine naturelle, les dibenzofuranes rencontrés en particulier dans les lichens, et les 2,2-diméthyl-2H-benzopyranes ou chromènes, tous deux connus pour leurs propriétés antifongiques et antibactériennes. L'oléfine du pyrane constitue un site privilégié de fonctionnalisation des pyranodibenzofuranes et permet notamment de moduler la lipophilie. Dans ce contexte noua avons mis au point une méthode de synthèse très simple en une étape permettant l'accès aux pyranodibenzofuranes. Ainsi, à partie de 2-hydroxydibenzofurane commercial, nous avons procédé à la préparation de l'éther propargylique, qui par simple chauffage conduit aux composés pyraniques fusionnés linéaires et angulaires, par réarrangement de Claisen. Nous avons ensuite entrepris la synthèse d'un certain nombre d'esters des diols cis et trans correspondants. Une étude systématique de l'activité antibactérienne sur Mycobacterium smegmatis a incité à poursuivre l'évaluation biologique des composés les plus actifs sur Mycobactérium tuberculosis. La deuxième partie décrit la synthèse d'analogues d'alcaloïdes antitumoraux isolés de diverses rutaceae appartenant au genre Zanthoxylum de série benzo[c]phénanthridine, tels la nitidine et la fagaronine. Nos objectifs portaient sur l'étude de l'influence du remplacement du cycle A par un cycle pyridinique et de l'introduction de chaînes dialkyllaminoalkylamines en position 6. Nous avons qinsi synthétisé des dérivés de série benzo[c][1,7]phénantrolines et benzo [c][1,8]phénanthrolines diversement substituées selon deux approches. La première met en jeu la cyclisation d'un intermédiaire de type benzyne généré par une base forte et permet l'accès à cinq benzo[c][1,7] et [1,8]phénantrolines diversement substituées. La seconde approche procède par couplage de biaryles de type Heck d'halogéno(iso)quinoléinylbenzamides en présence de palladium. Nous avons ainsi prépéré quatre diéthylaminoéthylaminobenzo[c][1,7] et [1,8]phénanthrolines via des inermédiaires benzo[c]phénanthrolin-6-ones et 6-chlorobenzo[c]phénanthrolines. Une étude de la cytotoxicité sur cellules de leucémie murine L1210 a été réalisée, la spécificité de cycle a également été déterminée. L'activité sur les topoisomérases I et II a été étudiée pour les composés les plus actifs.PARIS-BIUP (751062107) / SudocSudocFranceF

An Untargeted Metabolomic Approach for Microphytobenthic Biofilms in Intertidal Mudflats

International audienceMicrophytobenthic (MPB) biofilms in intertidal muddy sediments play important ecological functions in coastal ecosystems. These biofilms are mainly composed of epipelic diatoms but also prokaryotes, with a dominance of bacteria, which excrete diverse extracellular polymeric substances (EPS) according to their environment. While numerous studies have investigated the main components of these EPS matrices via traditional colorimetric assays, their fine composition, notably in specialized metabolites, is still largely unknown. A better chemical characterization of these MPB biofilms is necessary, especially regarding the numerous functions their chemical components play for microorganisms (e.g., motility, cell protection, defense mechanisms, and chemical communication), but also for coastal systems (e.g., primary production, sediment stabilization, larval settlement of some invertebrates with high economical value). An alternative approach to traditional analyses is the use of untargeted metabolomic techniques, which have not yet been applied to such MPB biofilms. The objectives of the present study were to (a) propose a protocol for metabolic fingerprinting by LC-MS and GC-MS for metabolites analysis in polar and non-polar fractions in MPB biofilms extracted from mudflat sediment and to (b) apply this protocol to a case study: the effect of light exposure on the metabolomic fingerprint of the MPB biofilm community. We compared three extraction methods using different mixes of solvents and selected a methanol/chloroform mix (1:1), which gave better results for both techniques and fractions. We then applied the selected protocol to our case study using a short-term light exposure experiment in aquaria (7 days). The present study is the first using a detailed untargeted metabolomic approach on MPB biofilms from mudflat sediment and will provide a solid baseline for further work in this area

A simple two steps ytterbium triflate‐catalysed preparation of 2,2‐dimethyl‐2h‐chromenes from salicylaldehydes and 2‐methylpropene

International audienceThe preparation of various 2,2‐dimethyl‐2H‐chromenes was achieved in two steps via an ytterbium triflate‐catalysed reaction between salicylaldehydes, trimethylorthoformate and 2‐methylpropene. From salicylaldehyde, two reaction products were characterised: 4‐methoxy‐2,2‐dimethylchroman and 2‐(1,3‐dimethoxy‐3‐methylbutyl)phenol. The former compound probably results from a Lewis acid‐catalysed [2+4] cycloaddition between the intermediate quinonemethide and 2‐methylpropene whereas the latter may occur via a reaction related to a carbonyl‐ene reaction between the quinonemethide and 2‐methylpropene. Both compounds were subjected to a catalytic acidic treatment leading to 2,2‐dimethyl‐2H‐chromene. Starting from various salicylaldehydes, the scope of this method was investigated

Nukuhivensiums, Indolo[2,3-a]quinoliziniums from the Marquesan Plant Rauvolfia nukuhivensis

International audienceThe first phytochemical inspection of the Marquesan endemic plant Rauvolfia nukuhivensis led to the isolation and structure characterization of two new indolo[2,3-a]quinolizinium derivatives named nukuhivensium and N₁₂-methyl-nukuhivensium. They feature an aromatic indolo[2,3-a]quinolizinium core, substituted at C-2 by a n-propyl group, which is unusual in this family of alkaloid derivatives. The structure elucidation was performed on the basis of NMR spectroscopy and especially by interpretation of 2D HMBC correlations. A biosynthetic pathway is proposed on the basis of known enzymatic transformations for this family of natural products. These compounds exhibited low antimicrobial activities

Synthesis and Antimicrobial Activities of Some Sulphur Containing Chromene Derivatives

A series of 3,3-dimethyl-3Hbenzothieno[3,2-f][1]-benzopyran analogues modified at the pyran 1,2-double bond were synthesized. The corresponding dihydro and (+/-)-cis-diol derivatives were converted into diacetate and cyclic carbonate upon acylation. The title compounds were characterized by spectroscopic analysis and screened for their antimicrobial activity in vitro

Laminariales Host Does Impact Lipid Temperature Trajectories of the Fungal Endophyte Paradendryphiella salina (Sutherland.)

International audienceKelps are colonized by a wide range of microbial symbionts. Among them, endophytic fungi remain poorly studied, but recent studies evidenced yet their high diversity and their central role in algal defense against various pathogens. Thus, studying the metabolic expressions of kelp endophytes under different conditions is important to have a better understanding of their impacts on host performance. In this context, fatty acid composition is essential to a given algae fitness and of interest to food web studies either to measure its nutritional quality or to infer about its contribution to consumers diets. In the present study, Paradendryphiella salina, a fungal endophyte was isolated from Saccharina latissima (L.) and Laminaria digitata (Hudson.) and its fatty acid composition was assessed at increasing salinity and temperature conditions. Results showed that fungal composition in terms of fatty acids displayed algal-dependent trajectories in response to temperature increase. This highlights that C18 unsaturated fatty acids are key components in the host-dependant acclimation of P. salina to salinity and temperature changes

Biosynthesis of azaphilones: a review

International audienceAzaphilones are fungal polyketide pigments bearing a highly oxygenated pyranoquinone bicyclic core which receive an increasing great deal of research interest for their applications on agroalimentary, dyeing, cosmetic, printing and pharmacy industries. Their biosynthetic pathways are not fully elucidated but thanks to recent genomic approaches combined to the increasing genome sequencing of fungi some of them have been recently unveiled. Here is the first review on the biosynthesis of azaphilonoids adressed from a genomic point of view