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。化学部的生命过程化学项目为芝加哥罗约拉大学的Graham Moran博士和堪萨斯大学的Audrey Lamb博士提供资金，以研究酶在核黄素关键生物合成中的作用方式。这个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杂志ASBMB Today共同撰写文章。这些OpEd风格的文章提供了职业发展的指导，可以加强科学界和促进包容性。这项研究项目是为了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种在自然界中无与伦比的酶活性。对这一途径进行了足够详细的研究，以确定每种酶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的异常脱甲酰化反应以及RibD的非常规多活性的机制。结构生物学研究(X射线结晶学)支持动力学和化学机理工作(稳定状态和稳定前状态)。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.