Collaborative Research: The Chemistry of Riboflavin Biosynthesis

核黄素（维生素B2）在所有生物体中都是必不可少的，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，化学部门的生命过程化学项目为格雷厄姆·莫兰博士（芝加哥洛约拉大学）和奥黛丽·兰姆博士（堪萨斯大学）提供资金，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催化的详细分子结构和化学步骤。在这里学到的基础科学知识可能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，博士。兰姆和莫兰合作为美国生物化学和分子生物学学会杂志《ASBMB Today》共同撰写文章。这些开放式文章为专业发展提供了指导，可以加强科学界并促进包容性。本研究项目旨在确定核黄素生物合成酶（特别是RibA， RibB和RibD）的结构-功能关系。核黄素生物合成包括自然界中无与伦比的五种酶活性。这一途径已经得到了足够详细的研究，以确定每种酶所进行的化学转化和酶的显著特征。本研究的重点是确定RibA和RibB异常脱甲酰基化反应的机制以及RibD的非常规多活性。动力学和化学机制的工作（在稳定和准稳定状态）是由结构生物学研究（x射线晶体学）支持的。这些结果为酶学领域和未来的生物催化研究提供了有价值的基础知识。该奖项反映了美国国家科学基金会的法定使命，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。

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.