The majority of compounds used to treat diseases come from a single group of organisms, the actinomycetes. This over-reliance on a single organism to produce the worlds drugs is a major problem for the development of compounds with alternative modes of action which can overcome and delay the onset of drug resistance. To address this problem we will form an international multi-disciplinary group of experts to bioprospect for biologically active natural products. The central aim of this programme is to start rapidly deriving novel drugs from non-actinomycete sources. We will isolate novel strains of the proven but not well-explored drug producers Xenorhabdus and Photorhabdus. These bacteria will be isolated from insect pathogenic nematodes and characterized taxonomically (WP1) and strains will be analyzed for the production of novel compounds (WP2). This library of compounds will then be tested against a broad set of targets including bacteria, fungi, protozoans, nematodes, insects, and mammalian cell cultures (WP3). The five most productive bacterial strains will then be fully sequenced and used to construct genomic libraries. These libraries will be used to generate recombinant clones in heterologous hosts, enabling fast and efficient biotechnological production of the bioactive compounds (WP4). To ensure efficient interactions and comparability of results, especially regarding the bioactivity data, training sessions will be organized with seminars and hands on experience for each of the groups at a central site (WP5). Robust patent stuctures will ensure efficient technology transfer to our industrial partners (WP6) and overall coordination of the scientific and training programs will be overseen by WP7.
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