Collaborative Research: The Chemistry of Riboflavin Biosynthesis

合作研究：核黄素生物合成的化学

• 批准号: 1904480
• 负责人: Graham Moran
• 金额: $ 32.5万
• 依托单位: Loyola University of Chicago
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1904480&HistoricalAwards=false
• 关键词: Collaborative; Research; Chemistry; Riboflavin; Biosynthesis

Riboflavin (Vitamin B2) is essential in all organisms, facilitating biological reactions that include cellular energy production, photosynthesis, DNA repair and response to oxidative stress. With this award, the Chemistry of Life Processes Program in the Chemistry Division provides funding to Dr. Graham Moran (Loyola University Chicago) and Dr. Audrey Lamb (University of Kansas) to study the ways enzymes function to in the critical biosynthesis of riboflavin. This collaborative project will systematically determine detailed molecular structures of and chemical steps catalyzed by these enzymes. The basic science knowledge learned here may provide strategies for the development of antimicrobial drugs. The experiments are the foundation for the training of undergraduate, graduate, and postdoctoral researchers at these two institutions. In addition, Drs. Lamb and Moran collaborate to co-write articles for the American Society of Biochemistry and Molecular Biology magazine ASBMB Today. These OpEd-style articles provide guidance on professional development that may strengthen the scientific community and promote inclusivity.This research project is undertaken to define the structure-function relationships of the enzymes of riboflavin biosynthesis (specifically RibA, RibB, and RibD). Riboflavin biosynthesis includes five enzymatic activities that are unparalleled in nature. This pathway has been studied in sufficient detail to establish the chemical transformations performed by each enzyme and the salient characteristics of the enzymes. The focus of this research is to define the mechanisms of the unusual deformylation reactions of RibA and RibB and the unconventional multi-activity of RibD. The kinetic and chemical mechanistic work (in the steady and pre-steady states) are supported by structural biology investigations (X-ray crystallography). The results provide valuable fundamental knowledge for the field of enzymology and future biocatalysis research.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.

核黄素（维生素B2）是所有生物体中必不可少的，促进生物反应，包括细胞能量产生，光合作用，DNA修复和对氧化应激的反应。有了这个奖项，化学部生命过程计划的化学提供资金给格雷厄姆·莫兰博士（洛约拉大学芝加哥）和奥黛丽·兰姆博士（堪萨斯大学）研究酶在核黄素关键生物合成中的作用方式。 该合作项目将系统地确定这些酶的详细分子结构和催化的化学步骤。在这里学到的基础科学知识可能会为抗菌药物的开发提供策略。这些实验是这两个机构培养本科生、研究生和博士后研究人员的基础。 此外，兰姆博士和莫兰博士还合作为美国生物化学和分子生物学学会杂志《今日ASBMB》撰写文章。这些专栏文章提供了专业发展的指导，可能会加强科学界和促进包容性。本研究项目的目的是确定核黄素生物合成酶（特别是RibA，RibB和RibD）的结构-功能关系。 核黄素的生物合成包括五个酶的活动，是无与伦比的性质。该途径已被研究足够详细，以建立由每种酶进行的化学转化和酶的显着特征。本研究的重点是确定RibA和RibB的不寻常的去乙酰化反应和RibD的非常规多活性的机制。动力学和化学机制的工作（在稳定和预稳定状态）的结构生物学研究（X射线晶体学）的支持。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

The Tenured Itch. Ready to treat your mid-career malaise?

终身之痒。

• 发表时间: 2019
• 期刊: ASBMB today
• 作者: Moran, Graham R;Lamb, Audrey L
• 通讯作者: Lamb, Audrey L

Perturbing the Movement of Hydrogens to Delineate and Assign Events in the Reductive Activation and Turnover of Porcine Dihydropyrimidine Dehydrogenase

扰动氢的运动来描述和分配猪二氢嘧啶脱氢酶的还原激活和周转事件

• DOI: 10.1021/acs.biochem.1c00243
• 发表时间: 2021
• 期刊: Biochemistry
• 影响因子: 2.9
• 作者: Beaupre, Brett A.;Forouzesh, Dariush C.;Butrin, Arseniy;Liu, Dali;Moran, Graham R.
• 通讯作者: Moran, Graham R.

The Interaction of Porcine Dihydropyrimidine Dehydrogenase with the Chemotherapy Sensitizer: 5-Ethynyluracil

猪二氢嘧啶脱氢酶与化疗增敏剂 5-乙炔尿嘧啶的相互作用

• DOI: 10.1021/acs.biochem.1c00096
• 发表时间: 2021
• 期刊: Biochemistry
• 影响因子: 2.9
• 作者: Forouzesh, Dariush C.;Beaupre, Brett A.;Butrin, Arseniy;Wawrzak, Zdzislaw;Liu, Dali;Moran, Graham R.
• 通讯作者: Moran, Graham R.

Evidence for the Chemical Mechanism of RibB (3,4-Dihydroxy-2-butanone 4-phosphate Synthase) of Riboflavin Biosynthesis.

• DOI: 10.1021/jacs.2c03376
• 发表时间: 2022-07-20
• 期刊: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
• 影响因子: 15
• 作者: Kenjic, Nikola;Meneely, Kathleen M.;Wherritt, Daniel J.;Denler, Melissa C.;Jackson, Timothy A.;Moran, Graham R.;Lamb, Audrey L.
• 通讯作者: Lamb, Audrey L.

Finding Ways to Relax: A Revisionistic Analysis of the Chemistry of E. coli GTP Cyclohydrolase II

寻找放松的方法：大肠杆菌 GTP 环水解酶 II 化学的修正分析

• DOI: 10.1021/acs.biochem.1c00511
• 发表时间: 2021
• 期刊: Biochemistry
• 影响因子: 2.9
• 作者: Smith, Madison M.;Beaupre, Brett A.;Fourozesh, Dariush C.;Meneely, Kathleen M.;Lamb, Audrey L.;Moran, Graham R.
• 通讯作者: Moran, Graham R.