(3p) New Biocatalysts for the Production of Renewable Chemicals: Bioinformatics and Molecular Simulation Studies On Fatty Acid Synthesis Enzymes

Being capable of designing enzymes to produce compounds not found in nature, or existing ones in greater quantities, is a desired goal in bioengineering. Computational molecular simulation and bioinformatics techniques can be used to study biological systems towards that end, with applications in fuels and specialty chemicals. Further, these techniques may also be directed toward designing new drug molecules and protein therapeutics. Work done for my doctoral dissertation is presented in this poster. Fatty acid and polyketide synthesis enzymes are the focus of our research as part of the NSF Engineering Research Center for Biorenewable Chemicals (CBiRC). Working with my major professor, Peter Reilly, my specific project is to find or design enzymes capable of catalyzing desired reactions. Toward that goal, we have classified enzymes into families through sequence analysis, and we have built a database containing known sequences and structures (www.enzyme.cbirc.iastate.edu). In a collaborative effort, thioesterases were studied experimentally based on our statistical and phylogenetic analyses. We recently conducted normal vibrational mode analysis and predicted three-dimensional structures of acyl carrier proteins. We are currently working on mixed quantum mechanics and molecular mechanics (QM/MM) simulations to find thioesterase reaction mechanisms and transition states.