P104: Identification of natural product pathways in cyanobacteria using post-genomics and secondary metabolomic profiling

Marine derived natural products have played and continue to play a pivotal role in the development of pharmaceutical agents, either directly or through structural inspiration. It is becoming increasingly recognized that a majority of these originate from the metabolic processes of bacteria, either free living or associated with macroorganisms such as sponges, tunicates and other invertebrates. One specific class of bacteria, the cyanobacteria, are exceptionally prosperous in their natural products. Cyanobacterial derived products have unique, nitrogen-rich and architecturally diverse structures which therefore have a high bioactive potential. Genome sequencing is revealing that microbial life, including marine cyanobacteria, have much more capacity for natural product biosynthesis than was appreciated from isolation studies. Sophisticated methods in mass spectrometric profiling, such as spectral maps, along with genomic analyses of different cyanobacterial strains, are helping to identify these new bioactive metabolites. Nevertheless many secondary metabolites are under strict environmental and epigenetic modes of regulation, while others are created constitutively. For a better understanding of secondary metabolite production, it is essential to evaluate and control environmental and epigenetic factors during cultivation, such as nitrogen, phosphorous, trace metals as well as growth temperature, light, pH, antibiotics and co-occurrence of other macro- and microorganisms, such as sponges, tunicates and heterotrophic bacteria. Taken together, the transcriptional activation of biosynthetic pathways is an exciting frontier in pharmaceutical drug discovery from natural sources.