Payne (1552355) The proposed research will provide fundamental understanding of the kinetics and thermodynamics by which a class of enzymes, known as glycoside hydrolases (GHs), catalyze the breakdown of biomass into sugars that can be processed further to fuels and chemicals. The knowledge thus obtained will guide the bioengineering of these enzymes to improve their efficiency and reduce the cost of renewable bio-based approaches to a sustainable energy future.
GHs break down crystalline biomass material such as cellulose or chitin by processivity - the repeated catalysis - or chewing away - of the bonds that hold the biomass material together. A number of factors related to the detailed structure and composition of both the GH and the biomass material affect the processivity. Although the processive mechanism has been the focus of numerous structural and biochemical studies, a clear connection between enzyme structure and processive function is still lacking. To this end, the proposed research focuses on developing a molecular-level understanding of the mechanisms governing GH processivity through molecular modeling and thermodynamic calculations backed by experimental biochemical characterization - the latter carried out with an international team of researchers. Although the work will primarily be directed at a model GH system utilizing chitinases, the goal will be to develop a generalized theory of GH processivity that will be assessed in the more common (and more complicated) cellulosic materials that will eventually form the basis of a renewable biomass fuel industry. The proposal also involves related elements of education and outreach - notably international research experiences for graduate students, dissemination of high performance computing tools to underserved research communities, and outreach to young girls aimed at exciting them about opportunities in science and engineering, especially in the biochemical area.
