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Structural and Functional Studies on Proteins


This proposal focused on the structural and functional characterization of enzymes involved in the biological synthesis of unusual natural products. A DNA-based approach to natural products, an approach where biosynthetic gene clusters are captured and heterologously expressed in host organisms has proven to be a powerful method for discovering new biologically active small molecules, new biosynthetic enzymes with unusual activity, and new signaling paradigms for small molecule-based signaling. The work proposed follows up on each of these themes and also proposes colony hybridization-based approaches to identifying potentially useful DNA sequences prior to heterologous expression. A genome wide scan with a synthetic library that amplifies the molecular diversity of the heterologously expressed libraries is also proposed. This scan, if successful, would provide functional annotation for the endogenous function of previously characterized small molecules. Finally, some polypeptides with antibiotic activity will be investigated.


Funded by the NIH National Center for Advancing Translational Sciences through its Clinical and Translational Science Awards Program, grant number UL1TR002541.