Amphiphilic Siderophores: Biosynthesis, Iron Uptake and Effect on Microbial Growth

几乎所有的细菌都需要铁来生长。 了解细菌从周围环境中获得铁的过程，为如何破坏铁的吸收过程提供了有价值的见解，并提出了限制有害微生物生长的潜在新策略。 这项提案的重点是找出独特的化合物称为铁载体是如何产生的，用于哈维氏弧菌和其他微生物的铁吸收，它们的产生与细菌菌落的形成和存活有关。 铁载体是由细菌产生的天然物质，其非常紧密地结合铁（III），在细菌的铁吸收中起着至关重要的作用。通过这些调查，研究生将接受将广泛的现代技术应用于多学科研究项目的培训。 反过来，研究生也将获得宝贵的经验，作为实验室本科生研究人员的导师，本科生将获得实践研究经验。有了这个奖项，化学系的生命过程化学项目资助加州大学圣巴巴拉的艾莉森巴特勒研究关键的两亲性铁载体的生物合成，如两性肠杆菌素，研究它们的物理性质，包括铁稳定常数和不同形式的两亲肠杆菌素的膜分配常数，研究存在于哈维氏弧菌基因组中的关键酯酶和外膜受体蛋白，它们被怀疑在铁摄取机制中是重要的，以及研究其他关键的两亲铁载体。 哈维氏弧菌是被广泛研究的群体感应模式生物，群体感应是细菌感知细胞密度的过程。 这些研究的发现将为酰化铁载体中脂肪酸在铁吸收过程中的重要性提供新的见解。

Nearly all bacteria require iron to grow. Understanding the process by which bacteria obtain iron from their surroundings provides valuable insight into how to disrupt the iron uptake process, and suggests potential new strategies to limit growth of deleterious microbes. The focus of this proposal is to find out how unique compounds called siderophores are produced for iron uptake in Vibrio harveyi and other microbes for which their production is tied to bacterial colony formation and survival. Siderophores are natural materials produced by bacteria that bind iron(III) very tightly playing a vital role in iron uptake by the bacterium. Through these investigations, graduate students will be trained in the application of a broad spectrum of modern techniques to a multidisciplinary research program. The graduate students will, in turn, also gain valuable experience as mentors to undergraduate researchers in the laboratory, and undergraduates will gain hands-on research experience.With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Alison Butler from the University of California, Santa Barbara to investigate the biosynthesis of key amphiphilic siderophores, such as the amphi-enterobactins, to investigate their physical properties including the ferric stability constants and membrane partitioning constants for different forms of the amphi-enterobactins, to investigate key esterases and outer membrane receptor proteins present in the genome of V. harveyi which are suspected to be important in the mechanism of iron uptake, as well as to investigate other key amphiphilic siderophores. V. harveyi is the widely studied model organism for quorum sensing, the process by which bacteria sense cell density. Discoveries from these investigations will provide new insights into the importance of the fatty acid in acylated siderophores in the iron uptake process.