Discovery and Mechanism of Biosynthetic Enzymes

生物合成酶的发现及其机理

• 批准号: 9484741
• 负责人: VAHE BANDARIAN
• 金额: $ 55.67万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-05-01 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9484741
• 关键词: Area; Biogenesis; Biological; Clinic; Complex; Development; Disease; Environment; Enzymes; Funding; Glean; Goals; Mediating; Metabolism; Molecular; National Institute of General Medical Sciences; Natural Products; Nucleic Acids; Nucleoside Q; Organism; Pathway interactions; Peptides; Physiology; Process; Research; Ribosomes; Role; Structure; Therapeutic Agents; Universities; Utah; base; enzyme mechanism; insight; polypeptide; small molecule; therapeutic development

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. !

项目摘要 生物合成途径富含酶促转化，在结构上产生 多种天然产物，例如二级代谢产物，改良的核酸和 修饰的肽。发现和理解这些分子基础 转变基于为发展深刻见解的努力，以使其对因素 要么相信许多疾病的过程，要么是它们在开发治疗剂中的使用。 NIGMS资助的两个主要资助的研究领域 犹他州的重点是（1）发现吡咯吡汀生物发生的分子基础 在多种二级代谢产物以及超修饰中发现的核心结构 碱，queuosine和（2）阐明了参与该酶的机制 核糖体合成后修饰的核糖体合成的生物合成途径 多肽（RIPPS）正在成为一组新的天然产品， 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。发现 这些酶的机械研究是作为此R35应用的一部分提出的。 呢