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Isolation and Identification of Plant-Specific Peptide Deformylase Inhibitors from Soil Microorganisms for Use as Broad-Spectrum Herbicides and Selectable Markers.
University of Kentucky Research in our laboratories has identified a potentially valuable competitor to existing technologies for broad-spectrum herbicides, as well as selectable markers in plant transformation vectors. This technology utilizes an essential plant gene, peptide deformylase, and peptide deformylase inhibitors. Peptide deformylase inhibitors behave as broad-spectrum herbicides and over-expression of chloroplast-localized peptide deformylase confers resistance to these inhibitors. Both of these technologies are owned and protected by the University of Kentucky (Patent #6,730,634, issued May 4, 2004). We have extensively characterized the broad-spectrum herbicidal characteristics of actinonin, a natural product with potent activity against peptide deformylase. Furthermore, we have engineered transgenic tobacco plants that exhibit complete resistance to this inhibitor. Actinonin is derived from a soil-borne Streptomyces, and although actinonin is highly selective towards peptide deformylase and has many desirable herbicidal traits, it is metabolized in plants at a rate that precludes its use as a broad-spectrum herbicide and it also inhibits bacterial peptide deformylase. Recently, an additional peptide deformylase inhibitor, also active against bacterial deformylase, was discovered from Bacillus subtilis, another soil-borne organism (1). We believe that the opportunity exists to isolate and identify additional natural products derived from soil-borne microorganisms capable of acting as potent plant-specific peptide deformylase inhibitors. Therefore, we propose to screen a large number of soil-derived microbial extracts as sources for plant specific peptide deformylase inhibitors using our combined expertise in the molecular biology and biochemistry of plant peptide deformylase, isolation of soil microorganisms, and isolation and purification of biologically-active compounds. |