S80: Merging Genomics, Mass Spectrometry, Bioinformatics and Biotechnology for Microbial Natural Product Discovery

Natural product discovery from microorganisms traditionally relies on the isolation of bioactive compounds from extracts of natural isolates grown under laboratory conditions. Obviously, this approach almost completely ignores all types of regulation involved in secondary metabolite formation and thus falls far short of identifying all compounds that a given strain is capable of producing. In most cases major products have been identified only. In the last decade, however, we have learned that microorganisms established as good natural product producers carry many more biosynthetic gene clusters in their genomes than compounds could be isolated from each species to date (1,2).

In the presentation I will discuss our approaches to combine genomic knowledge with gene inactivation studies and high resolution mass spectrometry coupled to bioinformatic tools with the aim to ultimately identify the complete secondary metabolome of each species (3-5). Studies towards deliberately inducing expression of biosynthetic gene clusters using regulatory genes will also be described and heterologous expression will be discussed as valid alternative (2,6). The developed technologies are basically applicable to every microorganism.