Discovery and Mechanism 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。 NIGMS资助的班达里安大学实验室的两个主要研究领域 犹他州专注于(1)发现吡咯嘧啶生物发生的分子基础 在各种次生代谢物中发现核心结构，以及在超修饰中 碱基、队列糖，以及(2)阐明参与 核糖体合成转录后修饰的生物合成途径 多肽(Ripps)是一类新兴的天然产物，具有 作为治疗剂的巨大潜力。这些途径通常利用复杂的自由基- 介导的酶转化，其机制尚不清楚。这一发现 并建议将这些酶的机理研究作为R35应用的一部分。 好了！

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 two major NIGMS-funded research areas in the Bandarian lab at the University of Utah focus on (1) discovering the molecular basis of biogenesis of the pyrrolopyrimidine core structure found in a variety of secondary metabolites, as well as in the hypermodified base, queuosine, and (2) elucidating the mechanism of enzymes involved in the biosynthetic pathways of ribosomally synthesized posttranscriptionally modified polypeptides (RiPPs), which are emerging as a new group of natural products with substantial potential as therapeutic agents. These pathways often utilize complex radical- mediated enzymatic transformations whose mechanisms are not known. The discovery and mechanistic studies of these enzymes are proposed as part of this R35 application. !