The goal of this Project is to chemically identify each of the 40+ secondary metabolites and their corresponding biosynthetic gene clusters that the fungus Aspergillus nidulans is capable of producing. As the chemical component of this multidisciplinary program project, we will use chemical techniques to identify the compounds that have thus far eluded characterization in A. nidulans. The era of genomics presents a whole new exciting approach for identifying new therapeutic leads. Traditional natural product drug discovery programs in the past few decades have demonstrated that fungi species such as Aspergillus have been a rich source of chemotherapeutic agents against a variety of diseases. The genomes of several Aspergillus species have recently been sequenced and interestingly the genomes revealed a potential to produce surprising large range of natural products many of which are currently unknown. More importantly the species produce compounds that are drastically different from each other suggesting that there is a wealth of natural products yet to be discovered. This discovery will in turn depend on advancements in tools manipulating Aspergillus genetics (Project 1) and understanding of Aspergillus secondary metabolite regulations (Project 2). Our component will involve analyzing the Aspergillus mutants created by the two subgroups. In addition because of our experience in polyketide synthase and nonribosomal synthetase, we will interact with the two subgroups to design experiments to elucidate these currently unknown secondary metabolites. Experimentally we will analyze secondary metabolites produced by A. nidulans strains provided by the Oakley group and Keller group using our Thermofinnigan LCQ. Methods will be developed to isolate newly discovered secondary metabolites and their chemical structures solved using NMR.
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