Discovery and mechanisms of biosynthetic enzymes

项目摘要 生物合成途径富含酶促转化， 多种天然产物，如次级代谢产物、修饰的核酸，以及 修饰肽。发现和理解这些的分子基础 变革是努力深入了解各种因素的基础， 或者掩盖许多疾病过程，或者它们在治疗剂开发中的用途。 拟议研究的重点将是阐明酶的机制， 采用彻底的转化来实现生物合成中的复杂转化 核糖体产生的和后修饰的肽。此应用程序将 利用生物化学，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 新的生物合成酶。

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.