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Biosynthesis of Deazapurine-containing metabolites

含脱氮嘌呤代谢物的生物合成

基本信息

批准号：
8260283
负责人：
VAHE BANDARIAN
金额：
$ 27.09万
依托单位：
UNIVERSITY OF ARIZONA
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-01-17 至 2014-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8260283
关键词：
6-pyruvoyltetrahydropterin synthase 7-deazaguanine Active Sites Anabolism Antibiotics Antiviral Agents Bacteria Biochemical Biochemical Genetics Cells Chemicals Civilization Enzymatic Biochemistry Enzymes Evolution Genes Genomics Goals Grant Guanosine Triphosphate Histidine-Specific tRNA Hormones Human In Vitro Knowledge Life Mediating Metabolism Methionine Methods Molecular Molecular Biology Nature Nucleoside Q Nucleosides Organism Pathway interactions Play Positioning Attribute Production Property Protein Biochemistry Proteins Purines Radial Reaction Relative (related person)Roentgen Rays Role Secondary to Streptomyces Structure Therapeutic Therapeutic Agents Toyocamycin Transfer RNA antitumor agent base design genome sequencing human disease improved insight interest member novel nucleoside oQ public health relevance purine reconstitution research study sangivamycin sepiapterin tetrahydrobiopterin tetrahydropterin tool tripolyphosphate

项目摘要

DESCRIPTION (provided by applicant): All organisms produce a host of compounds that are generally not required in primary metabolic processes, but play important regulatory functions. These secondary metabolites have been exploited by every civilization to enhance life and cure human diseases. We know these as hormones, antibiotics, antitumor agents, and antivirals. Since these metabolites can harm cells if produced in excess, or if present when a need for them does not exist, their production is often strictly regulated. An understanding of how cells synthesize and regulate the production of secondary metabolites is essential if one is to be able to exploit them as human therapeutic agents. Deazapurines are secondary metabolites that are derived from purines. This proposal outlines studies on the biosynthesis of deazapurine-containing secondary metabolites by bacteria. Our goal is to bring to fore the tools of genomics, molecular biology and enzymology to form the framework of how these metabolites are synthesized and to exploring the chemical transformations that underlies the biosynthesis of these molecules. PUBLIC HEALTH RELEVANCE: Deazapurine-containing compounds are widely distributed in nature and have been shown to have clinically useful activities. Our goal is to understand the chemical transformations that underlie biosynthesis of these compounds in an effort to synthesize additional molecules with improved properties.

描述（由申请人提供）：所有生物体都会产生大量化合物，这些化合物通常在初级代谢过程中不需要，但发挥重要的调节功能。每个文明都利用这些次生代谢物来增强生命和治疗人类疾病。我们知道它们是激素、抗生素、抗肿瘤药物和抗病毒药物。由于这些代谢物如果过量产生或在不需要它们时存在会损害细胞，因此它们的产生通常受到严格监管。如果要将细胞用作人类治疗剂，那么了解细胞如何合成和调节次生代谢物的产生至关重要。脱氮嘌呤是源自嘌呤的次级代谢产物。该提案概述了细菌生物合成含氮杂嘌呤的次级代谢产物的研究。我们的目标是突出基因组学、分子生物学和酶学工具，形成这些代谢物合成的框架，并探索这些分子生物合成基础的化学转化。公众健康相关性：含脱氮嘌呤的化合物在自然界中广泛分布，并已被证明具有临床有用的活性。我们的目标是了解这些化合物生物合成背后的化学转化，以努力合成具有改进性能的其他分子。