Biosynthesis of antifungal nucleoside antibiotics-Undergrad research supplement

项目摘要/摘要 这份行政补充资料将支持一名本科生为期10周的研究项目。这个 Parent R01项目旨在了解肽核苷(PN)抗真菌抗生素的生物合成 对多种病原真菌具有活性，并利用这一知识发现新的抗真菌药物。这个 拟议的夏季研究项目集中在亲本R01的目标3涉及NKS酰胺的部分 连接酶。具体地说，NIKS在化学酶法制备三七总皂苷中的应用潜力将是 调查过了。预计本科生将提纯NICK，化学合成~10个氨基 NICK的酸性底物类似物，并使用生成的化合物来测试底物特异性和潜力 NKS在化学酶法制备非天然三七总皂苷中的应用。这个项目将为学生提供 具有合成化学、生物有机化学和酶学方面的研究经验和常识 关于抗真菌抗生素的发现、生物合成和开发。因此，该项目将大大延长 本科生追求生物医学研究目标的研究经历 职业生涯。

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.