With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Keri Colabroy from Muhlenberg College and Dr. Larryn Peterson of Rhodes College to investigate an unstudied family of enzymes that cleave ring-shaped molecules called catechols. Catecholic rings are found in the woody tissue of plants to provide structure and strength. Nature refashions these rings into antibiotics and other bioactive materials. The complex relationship between enzyme structure and function is not well understood. This lack of understanding limits the ability to exploit the use of enzymes to make new natural products and degrade plant material into biofuels. The researchers generate new knowledge through the collaborative study of the enzyme-catalyzed reactions in real-time using small molecules carefully designed to expose the inner workings of catalysis. In addition to the direct mentorship of undergraduate students in faculty research labs, students transfer between institutions to experience the project from different perspectives. Part of the project is integrated into undergraduate coursework at each of the home institutions to give additional undergraduates the opportunity to conduct original research. Instructional videos of the established and emerging technologies and methods used in this research are published to a freely-accessible, online research archive for training of the next-generation science, technology, engineering and mathematics workforce both at the partner institutions and beyond.
This research project expands understanding of the extradiol dioxygenase mechanism by exploring structure and function for evolutionarily distinct, but representative members of a discreet topology (type IV) group within the vicinal-oxygen-chelate (VOC) superfamily. The synthesis of novel small-molecule substrates fuel the study of reaction kinetics, both in the pre-steady state and at equilibrium. This work also uses X-ray crystallography and mutagenesis to define the roles of active site residues and global kinetic modeling of substrate and mutant data to develop a mechanism. These experiments broaden the structural and kinetic understanding of extradiol dioxygenase mechanism, while also providing the opportunity to understand the extent of conservation versus permutation of dioxygenase mechanism as a function of topology within the VOC enzyme family.
