CONCEPT

Marine products discovery and development suffers one fundamental problem: There are excellent chemists who have discovered and structure-elucidated thousands of new compounds but only a very few of them has entered pre-clinical and clinical trials. This problem concerns in particular marine sponges, the best source for the discovery of novel bioactive molecules within the large group of marine invertebrates. In spite of the enormous efforts made in recent years, there is little prospect that the underlying main problems, namely the supply problem and the chemical synthesis of the often complex scaffolds will be solved. On the other hand, molecular biology, including marine molecular biology (“marine genomics”), biotechnology and bioengineering, is in a rapid development and has now reached a state where novel solutions of these prevailing problems can be developed. The first proof of concept has already been presented by consortium members (e.g., biochemical description of polyketide synthases with respect to biosynthetic gene clusters).  Our approach is therefore: To bundle existing excellence in classical marine natural products chemistry with existing excellence in marine molecular biology, biotechnology and bioengineering – presently fragmented (with respect to excellence, advanced equipment and trained staff) at different European academic institutions and companies – to develop trend-setting new methodologies for efficient and sustainable production of bioactive compounds – a new starting point for European biotech industry in an area of enormous economic potential and expected benefit for human that had been rather neglected in the past due to the opinion that there are only little chances for success. In essence, the long-term vision of this project is to provide and introduce to the market innovative beneficial bioactive compounds that meet the demands of the society in Europe. The critical mass of excellent scientists presently existing in a scattered way in Europe will be incorporated in a team, combining excellence in marine genomics, biotechnology and advanced chemistry. By that the international competitiveness in this area of research and development can be kept, a process which will also strengthen the connection between European member states. The salient feature of this large-scale, industry driven project is the molecular biological approach, in which it differs from projects based on traditional methods. We are convinced that by this approach it will be possible to exploit the tremendous potential of marine natural products in a sustainable manner for the benefit of our society. The goal of this 4-year integrating project is to exploit the unique ability of aquatic invertebrates, in particular sponges, as well as associated microorganisms to synthesize a large variety of bioactive compounds not available by chemical synthesis and shaped during millions of years of evolution that are of high value for human therapy. This integrating project aims (1) to introduce modern genomic techniques for a target-oriented screening to discover novel (lead) drug candidates and (2) to overcome the supply problem (by molecular-biology-based approaches), thus allowing a sustainable exploitation of aquatic molecular biodiversity. Marine sponges as sessile filter feeders have – as shown by molecular (cell) biological approach of one of the consortium PI’s - developed efficient defense mechanisms against viruses, bacteria or eukaryotic organisms. They are able to produce efficient antiviral, antimicrobial, and cytostatic compounds. Despite the large number and high structural variety of the bioactive secondary metabolites from sponges, only a very limited number of these compounds have been tested in clinical trials. Limited availability of larger quantities of starting material for extraction is one major obstacle for commercial development. To close this bottleneck it is the aim of this project to follow suitable, molecular-biology-based novel routes to obtain larger quantities of secondary metabolites from sponges, one of the most bioactive marine animal taxon and their associated microrganisms, as well as from bacteria from extreme marine environments, and to accelerate the development of such compounds.