The objectives of this multidisciplinary project are
To combine the knowledge in marine genomics with advanced methods in target-oriented drug screening and sustainable development for the discovery of novel natural products of biomedical/biotechnological interest from sponges, associated microorganisms, and marine bacteria, living in temperate or in extreme marine environments.
To use this knowledge for efficient primary and secondary screening, including molecular-biology-based approaches, and identification of bioactive metabolites and peptides/proteins, which besides neuroprotective, antimicrobial, and anti-aging activities will include hitherto neglected areas, such as anti-osteoporotic, anti-protozoan/anti-plasmodial, and innate-immune-response-modulating bioactivities.
To use advanced molecular biological and chemical techniques for the efficient isolation, structure elucidation and characterization of novel natural products, including secondary metabolites and bioactive peptides.
To develop and to introduce methods for fast identification of known compounds (replication) and for identification and characterization of minute amounts of natural products predicted by genome mining.
To identify, isolate and express new cDNAs (genetic “blueprints”) of commercial interest from sponge genomes, coding for enzymes/proteins involved in biosynthesis/biotransformation of bioactive molecules of therapeutical and/or biotechnical use (such as enzymes involved in carotenoid/retinoid biosynthetic pathways).
To identify and characterize cDNAs/proteins of commercial interest (such as light-responsive cryptochromes, heat/cold shock proteins, and enzymes/proteins involved in the accumulation of rare earth elements), isolated from extreme (darkness, high temperature, high pres-sure) aquatic environments, including deep-sea and cold-water sponges, psychrophilic and thermophilic (hydrothermal vent communities) bacteria, and bacteria involved in mineral deposition of deep-sea manganese nodules and seamount crusts.
To prepare metagenomic DNA libraries to access the whole aquatic bacteria diversity for genome mining (in silico identification of novel enzymes or other bioproducts for biomedical application).
To apply advanced metagenomic and biosynthetic prediction techniques to specifically tar-get genes and compounds of biomedical interest for sustainable production in a heterologous cultivable host (special focus: trans-AT polyketide synthases and protein enzymes).
To harness the natural biosynthetic machinery in a combined biotechnological and synthetic approach to generate natural product analogs for structure-activity relationship studies (precursor directed / combinatorial biosynthesis – mutasynthesis – modification of natural/unnatural products).
To identify the three-dimensional structural features of the bioactive natural and unnatural compounds synthesized through molecular modeling studies.
To develop, scale-up, and optimize the productivity of systems and fermentation processes for the sustainable large-scale production of selected bioactive compounds.
To undertake preclinical studies of selected potential drug leads identified in the course of the project.