The goal of this Project is to chemically identify each of the 40+ secondary metabolites and theircorresponding biosynthetic gene clusters that the fungus Aspergillus nidulans is capable of producing. As thechemical component of this multidisciplinary program project, we will use chemical techniques to identify thecompounds that have thus far eluded characterization in A. nidulans. The era of genomics presents a wholenew exciting approach for identifying new therapeutic leads. Traditional natural product drug discoveryprograms in the past few decades have demonstrated that fungi species such as Aspergillus have been a richsource of chemotherapeutic agents against a variety of diseases. The genomes of several Aspergillusspecies have recently been sequenced and interestingly the genomes revealed a potential to producesurprising large range of natural products many of which are currently unknown. More importantly the speciesproduce compounds that are drastically different from each other suggesting that there is a wealth of naturalproducts yet to be discovered. This discovery will in turn depend on advancements in tools manipulatingAspergillus genetics (Project 1) and understanding of Aspergillus secondary metabolite regulations (Project2). Our component will involve analyzing the Aspergillus mutants created by the two subgroups. In additionbecause of our experience in polyketide synthase and nonribosomal synthetase, we will interact with the twosubgroups to design experiments to elucidate these currently unknown secondary metabolites.Experimentally we will analyze secondary metabolites produced by A. nidulans strains provided by theOakley group and Keller group using our Thermofinnigan LCQ. Methods will be developed to isolate newlydiscovered secondary metabolites and their chemical structures solved using NMR.
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