Publishable Summary A number of biologically active compounds with varying degrees of action, such as antitumour, anticancer, cytotoxic, photoprotective, as well as antibiotic and antifouling properties, have so far been isolated from marine sources. The chemical and biological diversity of the marine environment is immeasurable and therefore is an extraordinary resource discovery of marine derived novel drugs. Hence, this project focused on the isolation of biologically active secondary compounds from marine sources. The work package is shared by groups of Turkey, Germany, Canada and China. Knowledge transfer will make this Project more extended and scientific. The work package of this Project divided into groups. Every group has their responsibility related with this Project. The aims of this project is given as following; a) Characterization of extracts and isolated compounds from marine-derived endophytic fungi in several screening platforms b) Bioactivity screening c) Establishing a blue mussel phenoloxidase inhibition assay as a powerful antifouling screening tool d) Establishing a blue mussel phenoloxidase inhibition assay as a powerful antifouling screening tool. The work package of Annex 1 was maintained by collecting seven marine samples from the Mediterrian and Egean Sea. Antimicrobial l antioxidant and cytotoxic activities of the samples were tested. Two of them showed strong cytoxic activity. Further investigations will continue for these two samples. Three of them showed antimicrobial activity and any substances showed significant antioxidant activity. Eight fungal endophytes could be isolated from six of the collected marine sources (Figure1) Ircinia Axinella Ircinia oros variabilis polypoides Penicillium sanguifluu m Bionectria ochraleuca Clonostach ys rosea Eurotium cristatum Acremoniu m sp. Bionectria ochraleuca Ascomycete sp. unspecified fungus Figure 1. During the cooperation program, we isolated 24 compounds from different marine-based endophytic fungi. To clarify, 13 compounds are isolated from Ircinia oros, 3 compounds are isolated rom Ircinia variabilis and 8 compounds are isolated from Axinella polypoides. . Further identification is pending and will be performed by HHU in the upcoming project period. Four of these twenty eight compounds are new. One of new compound was new metabolite from Pestialotiopsis sp. We will go further investigations about these 3 new compounds. Ascomycete sp. B. Ochraleuca Co-culture From an extract of the fungus Pestialotiopsis sp. the structure of a compound bearing an unusual cyclopropyl moiety (25, see figure 2) could be determined with various sepctroscopic methods. The compound was assigned as a new natural product. Figure 1. Structure of new metabolite (25) from Pestialotiopsis sp. And Canadian group work on total 181 bacteria were isolated from 41 samples, 26 of which were invertebrate samples. The isolated bacteria belonged to four different taxonomic classes, with the majority (55%) belonging to the class Actinobacteria (Figure 1). When classified to the genus level, the bacterial isolates could be assigned to 36 different genera(Figure 2). Among the Actinobacteria, bacteria belonging to the genera Streptomyces, Mycobacterium and Micromonospora were the most frequently isolated. Examining the similarity of the isolated bacteria to bacteria represented in the GenBank database revealed that 12.5% of isolates exhibited 96-<99% sequence identity with strains represented in this database. This suggests that these isolates represent novel species of bacteria thus may be of particular interest for the discovery of novel natural products. The remaining 87.5% of isolates exhibited >99% sequence identity to strains in the GenBank database, indicating that these isolates are related to previously described species, however, as natural product production is often strain specific, these microbes are also a valuable resource for natural product research.