EHPL

高效液相色谱法

• 批准号: 8170643
• 负责人: JAMES F PARSONS
• 金额: $ 0.29万
• 依托单位: BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8170643
• 关键词: Acids; Affect; Anabolism; Antibiotics; Biochemical; Chemistry; Chorismic Acid; Coenzyme A; Computer Retrieval of Information on Scientific Projects Database; Development; Environment; Erwinia; Funding; Gene Cluster; Grant; Human; Infection; Institution; Ligase; Metabolic; Organism; Pantoea agglomerans; Phenazines; Physical condensation; Production; Proteins; Pseudomonas; Reaction; Research; Research Personnel; Resources; Source; Structure; System; Therapeutic; United States National Institutes of Health; Vertebral column; Virulence; Work; antimicrobial; design; enzyme pathway; interest; killings; microorganism; research study

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. D-alanylgriseoluteic acid (AGA) is a broad spectrum antibiotic produced by Pantoea agglomerans (aka Erwinia herbicola), an enterobacterial species that is known to produce a number of interesting antimicrobial compounds. P. agglomerans appears to deploy AGA to kill other microorganisms in its local environment thus enhancing its competitiveness. AGA has been shown particularly effective against gram positive organisms. Certain strains of P. agglomerans are also capable of causing serious infections in humans. Thus we are interested not only in the chemistry of AGA biosynthesis from the standpoint of assessing the development of AGA like molecules as therapeutics, but also in terms of whether inhibition of AGA production affects the virulence of P. agglomerans. AGA is a phenazine antibiotic derived from the key metabolic intermediate chorismic acid. The biosynthesis of AGA involves a large gene cluster that encodes at least 15 proteins. Several of these are similar to the core phenazine pathway enzymes (that we have previously characterized) from Pseudomonas and that are responsible for the biosynthesis of the basic phenazine backbone. Many of the other steps in AGA biosynthesis are uncharacterized or poorly characterized. The subject of this work EhpF appears to be a phenazine CoA ligase that, we speculate, activates a phenazine substrate for a condensation reaction that modifies the phenazine ring system. Determination of the structure of EhpF will permit a comparison with other CoA liagses and will facilitate the design of specific biochemical experiments.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 D-丙氨酰灰甲苯酸（阿加）是由成团泛菌（Pantoea agglomerans）（又称Erwinia acglomerola）产生的广谱抗生素，所述成团泛菌是已知产生许多有趣的抗微生物化合物的肠细菌物种。聚团青霉似乎利用阿加杀死其局部环境中的其它微生物，从而增强其竞争力。 阿加已被证明对革兰氏阳性微生物特别有效。成团变形杆菌的某些菌株也能够在人类中引起严重感染。 因此，我们不仅从评价阿加样分子作为治疗剂的发展的角度对阿加生物合成的化学感兴趣，而且还对抑制阿加产生是否影响成团变形杆菌的毒力感兴趣。阿加是一种吩嗪类抗生素，来源于关键的代谢中间体氯酸。阿加的生物合成涉及一个大的基因簇，编码至少15种蛋白质。其中几种类似于来自假单胞菌的核心吩嗪途径酶（我们先前已表征），并且负责基本吩嗪骨架的生物合成。阿加生物合成中的许多其它步骤未被表征或表征较差。这项工作的主题EhpF似乎是一个吩嗪CoA连接酶，我们推测，激活吩嗪底物的缩合反应，修改吩嗪环系统。EhpF结构的确定将允许与其他CoA连接进行比较，并将有助于设计特定的生化实验。