P132: Search for molecular inducers of secondary metabolite production in actinomycetes

Monday, August 2, 2010
Pacific Concourse (Hyatt Regency San Francisco)
Don Hahn, Discovery Biology, Dow AgroSciences, Indianapolis, IN, Nadaraj Palaniappan, Bioprocess Research & Development, Dow AgroSciences, Indianapolis, IN and Quanbo Xiong, Discovery Chemistry, Dow AgroSciences, Indianapolis, IN
It is known from genomic sequencing that actinomycetes have many cryptic biosynthetic pathways which are not expressed under normal fermentation conditions.  The ability to induce these cryptic biosynthetic pathways would provide a means to discover novel bioactive metabolites from actinomycetes.  It has been demonstrated that sub-inhibitory concentrations of antibiotics can induce gene expression in bacteria, however, this technique has not been extensively evaluated in actinomycetes.  We tested a wide range of antibiotics for their ability to induce novel metabolites in a variety of actinomycete isolates.  The metabolites produced were assessed by LC-MS based chemical fingerprinting.  In Streptomyces avermitilis, oligomycin A was over expressed by treatment with ethanol or addition of bacitracin or other antibiotics.  In addition, several cryptic metabolites were induced in S. avermitilis.  In our hands, sub-inhibitory concentrations of antibiotics were able to over express metabolites as well as induce cryptic metabolites in a variety of actinomycetes.  Methods used and implications for novel metabolite discovery will be discussed.