Collaborative Research: The Chemistry of Riboflavin Biosynthesis

This research project will be undertaken to define the structure-function relationships of the enzymes of riboflavin biosynthesis.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 proposal is the mechanisms of the unusual deformylation reactions of RibA and RibB and the unconventional multi-activity of RibD will be defined. The kinetic and chemical mechanistic work (in the steady and pre-steady state) will be supported by structural biology investigations (X-ray crystallography). The results will provide valuable fundamental knowledge for the field of enzymology and future biocatalysis research.The basic science knowledge learned here may provide strategies for antimicrobial drug development. 
 
 Riboflavin (Vitamin B2) is essential in all organisms. facilitating biological reactions that include cellular energy production. photosynthesis. DNA repair and in 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 mechanisms of enzymes that are critical for the biosynthesis of riboflavin.This collaborative project will systematically elucidate detailed molecular structures of and chemical steps catalyzed by these enzymes. The experiments proposed are the foundation for training of undergraduate. graduate. and postdoctoral researchers at these two institutions.In addition. Drs. Lamb and Moran will collaborate to co-write articles for the American Society of Biochemistry and Molecular Biology magazine ASBMB Today. These OpEd-style articles will provide guidance on professional development that will strengthen the scientific community and promote inclusivity.