We are only beginning to understand the astounding bacterial diversity living in and on plants and animals, including humans. About half of the proposed bacterial phyla have never been cultured in the laboratory, and our only window into their existence comes from sequencing data. This presentation will highlight two projects that illustrate the potential of host-associated bacteria as sources of new bioactive natural products and biosynthetic pathways. First, I will describe my work on the non-heme iron-dependent halogenases, unusual bacterial enzymes that can catalyze halogenation of unactivated carbon centers in natural product biosynthesis. Our crystal structure of the model halogenase SyrB2 from Pseudomonas syringae revealed a surprising iron coordination motif and allowed us to propose a new mechanism for this class of biosynthetic enzymes. The second half of the talk will focus on sequence-guided discovery of natural products from bacteria associated with the model invertebrate Ciona intestinalis. This approach to natural product discovery can reveal ecologically relevant metabolites that may not be produced under laboratory conditions and links product discovery to the responsible biosynthetic machinery.
Prof. M.G. Finn (404-385-0906)