Implantation of the VNS device is usually done as an outpatient procedure

racterized from O. griseum UBOCC-A-114129. These compounds have already been described from terrestrial O. fuscum, O. griseum, and P. gallicola n. sp.. However, to the best of our knowledge, this is the first report of the production of fuscin and its derivatives by a marine fungus in the meantime and the antimicrobial activity of secofuscin and dihydrosecofuscin. The production of fuscin, dihydrofuscin, dihydrosecofuscin, and secofuscin occurred after the fungus has completed his growth and can thus be qualified as secondary metabolites. Secondary metabolites are small molecular weight molecules produced by microorganisms to compete with environmental stressing conditions such as temperature, pressure, salinity, and those arising from other microorganisms. Some of them could be beneficial as antimicrobial or antitumor activities, whereas other could be deleterious to humankind . Dihydrosecofuscin has been previously described as a biosynthetic precursor of fuscin. It was here the most produced metabolite and appeared to co-occur with the other derivatives. This is the first report on their co-production in an Oidiodendron species. Although fuscin and its derivatives appear as the major metabolites produced during the stationary phase, their ecological role remains to be clarified. The chemical structure of those compounds suggested a polyketide, a terpenoid structure, or a hybrid of both, as suggested by Birch and his colleagues. Previous investigation of genes coding polyketides synthases and terpene synthases revealed the unique presence of polyketide synthases in the O. griseum UBOCC-A-114129 genome and thus likely highlighted the polyketide nature of the bioactive metabolites produced by this isolate. Although fuscin and dihydrofuscin were previously investigated for antimicrobial activities, no data were available regarding dihydrosecofuscin and secofuscin. MIC values reflected a weak but significant antimicrobial activity. A ONX-0914 bactericidal mode of action was also revealed against various Gram-positive bacterial targets. Finally, dihydrosecofuscin showed in vitro inhibition of kinase activity against CLK1. Penicillium terrestre, a marine fungus isolated from marine sediment, has also been described for its anti-kinase activity. A 35% inhibition of tyrosine kinases was observed when incubated with 3 g/mL of the bioactive metabolite terrestrol G synthetized by Penicillium terrestre. Therefore, dihydrosecofuscin weakly inhibited CLK1 activity with an IC50 of 15.6 g/mL. Since this kinase has been reported to be a relevant target for Alzheimer’s disease treatment, dihydrosecofuscin may provide a structural pattern for developing new therapeutic drugs. 4. Materials and Methods 4.1. Fungal Isolation and Identification Isolation and identification of the fungal isolate selected in this study has been described in an earlier report. Briefly, sediment samples were plated onto five low nutrient media with or without sea salts, at different temperatures and at different hydrostatic pressures. Subcultures of each colony were performed to obtain pure cultures. Purified isolates were then cryo-preserved on beads at -80 C. The sequence analysis of 18S rDNA and internal transcribed spacer genetic markers revealed O. griseum as the nearest relative of our strain with 99% of similarity in GenBank database. Then, the strain was subcultured onto PDA for 14 days at 25 C. Six 250 mL Erlenmeyer flasks, containing 50 mL of Potato Dextrose Broth PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19840930 PDB compleme