Discovery and characterization of new bioactive compounds through genome-based bioprospecting of marine bacteria

A large library of marine actinobacteria (ca 9.000 strains) isolated from sediments, sponges and neuston layer in the Trondheim fjord (Norway) has been assembled. Earlier partial characterization of the library revealed its significant potential for disco very of novel natural products with anti-infective and anti-cancer properties. However, as revealed by draft genome sequencing and analyses of 15 bacterial species from this library, the hidden potential of these bacteria is much larger. Over 70 unique ge ne clusters for biosynthesis of potentially novel bioactive compounds have been revealed by this approach. These genes, however, remain silent, and special techniques must be used to activate them in order to produce, purify and characterized these compou nds. In the proposed project we plan to obtain draft genome sequences for 30 additional rare isolates. The genomes will be scanned for the presence of unique genes for natural product biosynthesis using an innovative software. Cloning and heterologous ex pression of the identified unique biosynthetic genes in specially designed bacterial host will be achieved, and recombinant bacteria obtained will be screened for anti-microbial and anti-cancer activities. "Hits" obtained will be followed up by identific ation of active compounds, production, purification and structure elucidation. Purified compounds will be extensively tested for in vitro activity against panels of microbial and tumor cells. Those compounds which will be proven novel and passed the in vi tro tests will be available for licensing/further development by biotech or pharma companies.