Marine organisms, in particular sponges and their associated microorganisms, are an inexhaustible source of novel bioactive (lead) compounds for biomedical application. Industrial exploitation of this natural resource using traditional approaches is, however, hampered, with a few exceptions, by unsolvable supply problems - despite of numerous efforts in the past. Therefore, there is, very likely, only one way: to start from the genes encoding the bioproducts, or their biosynthetic pathways, to sustainably obtain the active molecules in sufficient amounts. The aim of the presented industry-driven integrating project is to combine the knowledge in marine genomics, chemogenetics and advanced chemistry to produce recombinantly prepared novel secondary metabolite (lead) compounds and analogous from them, as well as pharmacologically active peptides, and to bring them up to the pre-clinical, and hopefully also to the clinical studies. This ambitious approach is based on breakthrough discoveries and the results of previous successful EU projects of members of the applying consortium, including European leaders (or worldwide leaders) in marine (sponge) genomics, metagenomics (polyketide synthase clusters), combinatorial biosynthesis and marine natural product chemistry/structure elucidation. This multidisciplinary project, driven by high-tech genomics-based SMEs with dedicated interest in bringing marine-biotechnology-derived products to the market, will also involve the discovery and sustainable production of bioactive molecules from hitherto unexploited extreme environments, such as hydrothermal vents and deep-sea sources, and the expression/scale-up of unique enzymes/proteins of biomedical and biotechnological interest. The molecular-biology-based strategies developed in this project for a sustainable exploitation of aquatic molecular biodiversity will further strengthen the international position and effectiveness of European (SME-based) blue biotechnology industry.