CAREER: Peptidic Natural Products in Research and Education

在化学部生命过程化学项目的支持下，来自佐治亚理工学院的Vinayak Agarwal正在研究多肽的酶修饰成生物活性有机分子。修饰的多肽有机分子在化学、药理学和农业中的重要性怎么强调都不为过。这些多肽分子通常是由基因编码的酶作用于底物多肽而产生的。该项目旨在发现和生化研究多肽修饰酶，并了解这些酶是如何识别和结合底物多肽的。这将使研究生在遗传学、生物化学、分子生物学和分析化学程序方面获得有价值的培训。该项目还旨在主办机构的综合课程改革，本科生将接受微生物学和分析化学实验的理论和实践培训，旨在激励他们留住科学研究生课程，从而丰富国家未来受过技术培训的劳动力。多肽和蛋白质的酶修饰继续提供新的化学反应。从挖掘细菌基因组和亚基因组入手，本项目将重建生物合成酶的生化活性，并对多肽修饰酶催化的反应和底物范围提出质疑。特别令人感兴趣的是对分子间多肽-蛋白质相互作用的原子水平的理解，这些相互作用是上述化学修饰的基础。利用多种生物物理技术，对纯化的底物多肽和纯化的修饰酶之间的相互作用机制进行了探讨。生物物理研究将得到生化实验的证实，目的是加深对分子间识别规则的理解。这些努力有可能提供新的通用生物催化剂，允许对多肽底物进行量身定制的修饰。与此同时，在主办机构的物质和人员支持下，将为本科生开发新的课程，提供旨在从细菌来源中发现多肽天然产品的最先进的基于质谱学的工作流程的指导，以及科学交流和写作方面的培训。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

With the support of the Chemistry of Life Processes Program in the Division of Chemistry, Vinayak Agarwal from Georgia Institute of Technology is studying the enzymatic modification of peptides into bioactive organic molecules. The importance of modified peptidic organic molecules in chemistry, pharmacology, and agriculture cannot be overstated. These peptidic molecules are typically produced by genetically encoded enzymes acting upon a substrate peptide. The proposed project is aimed at the discovery and biochemical study of peptide modifying enzymes, and understanding how these enzymes recognize and bind to the substrate peptides. This pursuit will allow graduate students to gain valuable training in genetics, biochemistry, molecular biology, and analytical chemistry procedures. This project also aims at integrated curriculum innovation at the host institution wherein undergraduate students will receive theoretical and hands-on training in microbiology and analytical chemistry experiments with the aim to motivate their retention in postgraduate programs in science, thusly enriching the nation’s future technically trained workforce.The enzymatic modification of peptides and proteins continues to furnish new chemical reactions. Starting with the mining of bacterial genomes and metagenomes, this project will reconstitute the biochemical activities of biosynthetic enzymes and query the reactions catalyzed by and the substrate scope for the peptide modifying enzymes. Of particular interest is the atomistic-level understanding of intermolecular peptide-protein interactions that underlie the above-mentioned chemical modifications. Using a variety of biophysical techniques, the mechanism of interactions between purified substrate peptides and purified modification enzymes will be queried. The biophysical studies will be corroborated with biochemical experiments, with the aim to develop a deeper understanding of the rules of intermolecular recognition. These efforts have the potential to provide new general-purpose biocatalysts that allow for tailored modification of peptidic substrates. Concomitantly, with material and personnel support from the host institution, new coursework for undergraduate students will be developed which will provide instruction in state-of-the-art mass spectrometry-based workflows aimed towards the discovery of peptidic natural products from bacterial sources, together with training in scientific communication and writing.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.