Biosynthesis of antifungal nucleoside antibiotics-Undergrad research supplement

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Project Summary/Abstract This administrative supplement will support a 10-week long research project for an undergraduate student. The parent R01 projects aims to understand the biosynthesis of peptidyl nucleoside (PN) antifungal antibiotics that are active against multiple pathogenic fungi and to discover novel antifungal agents using this knowledge. The proposed summer research project focuses on the part of Aim 3 of the parent R01 involving the NikS amide ligase enzyme. Specifically, the potential for use of NikS in the chemoenzymatic preparation of PNs will be investigated. It is anticipated that the undergraduate student will purify NikS, chemically synthesize ~10 amino acid substrate analogs of NikS and use the resulting compounds to test the substrate specificity and the potential usage of NikS for chemoenzymatic preparation of unnatural PNs. This project will provide the student with research experience in synthetic chemistry, bioorganic chemistry and enzymology as well as general knowledge about antifungal antibiotics discovery, biosynthesis and development. Thus, the project will significantly extend the research experience of the undergraduate student towards her goal of pursuing a biomedical research career.