Bioinorganic Chemistry of Catechol-Amine Siderophores and Biomimetic Analogs: Chirality of Iron Coordination and Bacterial Uptake

儿茶酚胺铁载体和仿生类似物的生物无机化学：铁配位的手性和细菌摄取

• 批准号: 2108596
• 负责人: Alison Butler
• 金额: $ 50.4万
• 依托单位: University of California-Santa Barbara
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-11-01 至 2024-10-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2108596&HistoricalAwards=false
• 关键词: Bioinorganic; Chemistry; Catechol; Amine; Siderophores

With the support of the Chemistry of Life Processes Program in the Chemistry Division, Dr. Alison Butler from the University of California-Santa Barbara will investigate compounds called siderophores that bacteria produce to obtain iron, an essential nutrient for the growth of most bacteria. Siderophores, which is Greek for iron (sideros)-liking (phore), bind iron with very high affinity and transport it into the cells of bacteria, which is a process essential for the life of the bacteria. Dr. Butler and her team will focus on the study of the effect of chirality, i.e. their left handed or right handed shape, on the iron uptake by the bacteria. The new knowledge gained from this study may be beneficial to the control of deleterious microbial infections if the chirality could be used to disrupt the process of iron uptake by microbes. The graduate and undergraduate students involved in the research will acquire a broad education and training in bioinorganic and bioorganic chemistry as well as a foundation in interdisciplinary research, likely to be useful in their future careers. The PI and her students will also engage in outreach workshops through UCSB’s Center for Science and Engineering Partnerships (CSEP) and the Summer Institute in Science and Math (SIMS) to assist undergraduates in developing effective scientific communication skills and to assist mentors in developing effective mentoring strategies.The research supported by this award focuses on a new combinatoric suite of tris-catechol siderophores, tris-(2,3-DHB--L/D-CAA--L-Ser), in which DHB if dihydroxybenzoate and CAA is the cationic amino acid L/D-Lys, L/D-Arg or L/D-Orn. The diastereomeric pairs of each siderophore form complexes with Fe(III), which are enantiomeric. The specific aims of the research are (i) to elucidate the structural and molecular characteristics that govern the chirality of the Fe(III)-enantiomeric complexes, (ii) to investigate the exchange of Fe(III) between diastereomeric siderophores, including the effect of the nature of the CAA on the exchange process; and 3) to investigate the influence of the stereochemistry of Fe(III)-[tris(2,3-DHB--L/D-CAA--L-Ser)] on microbial growth. The new siderophores will be isolated, relevant synthetic analogues will be synthesized and both will be structurally characterized. Circular dichroism, racemic crystallization, and molecular modeling will be carried out on the Fe(III)-siderophore complexes and appropriate synthetic analogues. The kinetics of Fe(III) exchange will be followed by circular dichroism. Microbial growth will be monitored in disk-diffusion bioassays.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

在化学过程的化学过程的支持下并将其转移到细菌的细菌中，以使Butler博士及其团队的研究将细菌的效果（通过细菌的铁吸收）。控制有害的微生物感染是否可以使一些研究的研究生和本科生的摄入过程破坏了一些研究生，这将获得广泛的教育和培训，可能对他们的未来职业有用。策略研究的成对与Fe（iii）的研究形成了（i）是（i），以阐明Fe（iii） - 抗剂量复合物的结构和分子特征，（ii）III），包括对非对象体siderophores之间，包括包括的效果交换过程中的自然； 3）Fe（III） - [TRIS（2,3-DHB-L/D-CAA-L-SER）]合成的圆形二色性在磁盘扩散生物测定中受到监控。该奖项反映了NSF'Sf'sf'sfly fly使命，并使用基金会的知识分子优点和更广泛的影响评估标准，值得支持评估。

项目成果

Mining elements of siderophore chirality encoded in microbial genomes

挖掘微生物基因组中编码的铁载体手性元素

• DOI: 10.1002/1873-3468.14539
• 发表时间: 2023
• 期刊: FEBS Letters
• 影响因子: 3.5
• 作者: Butler, Alison;Jelowicki, Aneta M.;Ogasawara, Haley A.;Reitz, Zachary L.;Stow, Parker R.;Thomsen, Emil
• 通讯作者: Thomsen, Emil

Ruckerbactin Produced by Yersinia ruckeri YRB Is a Diastereomer of the Siderophore Trivanchrobactin Produced by Vibrio campbellii DS40M4

由鲁克氏耶尔森菌 YRB 产生的 Ruckerbactin 是由坎贝氏弧菌 DS40M4 产生的铁载体 Trivanchrobactin 的非对映异构体

• DOI: 10.1021/acs.jnatprod.1c01047
• 发表时间: 2021
• 期刊: Journal of Natural Products
• 影响因子: 5.1
• 作者: Thomsen, Emil;Reitz, Zachary L.;Stow, Parker R.;Dulaney, Kalana;Butler, Alison
• 通讯作者: Butler, Alison

Marine Microbial Siderophores: Reactivity and Structural Diversity

海洋微生物铁载体：反应性和结构多样性

• 发表时间: 2022
• 期刊: The chemist
• 作者: Alison Butler