One of the key revelations to arise from the large-scale sequencing of bacterial genomic DNA is that traditional approaches used for the discovery of natural products only provide functional access to a small fraction of the natural product biosynthetic gene clusters present in nature.  The sequencing of DNA extracted directly from soil samples indicates that as yet uncultured soil microbes outnumber their cultured counterparts by at least two to three orders of magnitude.  This uncultured majority no doubt produces secondary metabolites that could serve as molecular probes of biological processes and therapeutic agents. Uncultivated microorganisms are a very attractive source of potentially new natural products, but they are not amenable to the traditional approaches used to characterize natural products from microbes grown in pure culture.  Although there appears to be no easy way to culture this collection of unstudied microorganisms, it is possible to isolate large fragments of microbial DNA directly from environmental samples and clone this DNA into model bacterial systems in the lab.  We are using both functional and sequence-based screening strategies to access natural products from large environmental DNA libraries.  New metabolites and biosynthetic enzymes discovered using these approaches will be discussed.

Culture independent approaches for the discovery of new bacterial metabolites

239th National Meeting (2010)

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