Discovery and mechanisms of biosynthetic enzymes

项目总结 生物合成途径富含从结构上产生的酶转化。 各种天然产物，如次生代谢物、修饰核酸和 修饰的多肽。发现和理解这些的分子基础 转型是开发对以下因素的深刻见解的努力的基础 要么掩盖了许多疾病过程，要么掩盖了它们在治疗药物开发中的应用。 拟议研究的重点将是阐明酶的作用机制 在生物合成中采用自由基转化来实现复杂转化 核糖体产生和翻译后修饰的多肽。此应用程序将 利用生化、结构和光谱技术来探测 这些酶的机制，建立结构-功能关系，并发现 新型生物合成酶。

PROJECT SUMMARY Biosynthetic pathways are rich in enzymatic transformations that produce structurally diverse natural products, such as secondary metabolites, modified nucleic acids, and modified peptides. Discovering and understanding the molecular basis for these transformations underpins efforts towards development of deep insights into factors that either belie many disease processes, or their use in development of therapeutic agents. The focus of the proposed studies will be elucidating the mechanisms of enzymes that employ radical transformations in effecting complex transformation in the biosynthesis of ribosomally produced and posttranslationally modified peptides. This application will make use of biochemical, structural, and spectroscopic techniques to probe the mechanisms of these enzymes, establish structure-function relationships, and to discover novel biosynthetic enzymes.