EHPL

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 D-丙氨酰灰解酸(AGA)是一种广谱抗生素，由聚集性泛细菌(又名草本欧文氏菌)产生，是一种肠道细菌，能产生许多有趣的抗菌化合物。聚集性巴氏杆菌似乎利用AGA杀死其本地环境中的其他微生物，从而增强其竞争力。AGA已被证明对革兰氏阳性菌特别有效。聚集性巴氏杆菌的某些菌株也能在人类中引起严重感染。因此，我们不仅从评估AGA类分子作为治疗药物的发展的角度对AGA的生物合成化学感兴趣，而且还从抑制AGA的产生是否影响聚集性巴氏杆菌的毒力的角度对其感兴趣。AGA是一种吩嗪类抗生素，来源于关键的代谢中间产物分枝酸。AGA的生物合成涉及一个大的基因簇，编码至少15个蛋白质。其中几个类似于来自假单胞菌的核心吩嗪途径酶(我们之前已经表征过)，它们负责吩嗪基本主干的生物合成。AGA生物合成中的许多其他步骤都没有特征或特征不佳。这项工作的主题EhpF似乎是吩嗪CoA连接酶，我们推测，它激活吩嗪底物进行缩合反应，从而改变吩嗪环系统。确定EhpF的结构将允许与其他CoA实验进行比较，并将有助于设计特定的生化实验。

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.