Marine organisms, in particular sponges and their associated microorganisms, are an inexhaustible sourceof novel bioactive (lead) compounds for biomedical application. Industrial exploitation of this natural resourceusing 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 genesencoding the bioproducts, or their biosynthetic pathways, to sustainably obtain the active molecules in sufficientamounts. The aim of the presented industry-driven integrating project is to combine the knowledge in marinegenomics, chemogenetics and advanced chemistry to produce recombinantly prepared novel secondarymetabolite (lead) compounds and analogous from them, as well as pharmacologically active peptides, and tobring them up to the pre-clinical, and hopefully also to the clinical studies. This ambitious approach is basedon breakthrough discoveries and the results of previous successful EU projects of members of the applyingconsortium, including European leaders (or worldwide leaders) in marine (sponge) genomics, metagenomics(polyketide synthase clusters), combinatorial biosynthesis and marine natural product chemistry/structureelucidation. This multidisciplinary project, driven by high-tech genomics-based SMEs with dedicated interest inbringing marine-biotechnology-derived products to the market, will also involve the discovery and sustainableproduction of bioactive molecules from hitherto unexploited extreme environments, such as hydrothermalvents and deep-sea sources, and the expression/scale-up of unique enzymes/proteins of biomedical andbiotechnological interest. The molecular-biology-based strategies developed in this project for a sustainableexploitation of aquatic molecular biodiversity will further strengthen the international position and effectiveness ofEuropean (SME-based) blue biotechnology industry.