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. !

项目概要 生物合成途径富含酶促转化，可产生结构性的 多样化的天然产物，例如次级代谢产物、修饰核酸和 修饰肽。发现并理解这些的分子基础 转型支撑着深入洞察影响因素的努力 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用途。 伦敦大学班德里安实验室由 NIGMS 资助的两个主要研究领域 犹他州重点研究（1）发现吡咯并嘧啶生物发生的分子基础 在各种次生代谢物以及超修饰中发现的核心结构 碱基、queuosine，以及（2）阐明参与该过程的酶的机制 核糖体合成转录后修饰的生物合成途径 多肽（RiPP），作为一类新的天然产物而出现 作为治疗剂的巨大潜力。这些途径通常利用复杂的自由基 介导的酶促转化，其机制尚不清楚。发现 提议对这些酶进行机理研究作为 R35 应用的一部分。 ！