The main objective of this project is to develop a platform technology, Nanopore Enhanced Enzyme Device (NEED), for the production of enantiomerically pure (i.e. chiral specific) drug intermediates. The enzyme is to be immobilized on a nanopore support whose pore morphology and surface modifications will be specifically designed for further enhancing the enzyme's activity and selectivity.
The specific aims of this project are: A.1 Lipase Immobilization with nanopore silica-chitosan composite as a bioreactor A.2 Enhancing Enzyme Performances by modifying nanopore support and controlling water activity A.3 Achieving Reaction and Separation Synergistically in NEED In accordance with the three specific aims set above, we propose to accomplish the following technical milestones during the course of this project: (1) Immobilizing a lipase onto silica-chitosan nanopore composite while maintaining its activity and selectivity; (2) Creating open channel structure and high surface area in the nanocomposite through engineered pore structures to significantly enhance the reaction rate of the attached lipase; (3) Increasing the hydrophobic-hydrophilic interfacial area, by incorporating surface modification ligands, within the composite to further enhance lipase's activity; (4) Using the swelling ratio of the chitosan phase to control and fine tune water activity surrounding the lipase; (5) Enhancing the efficiencies of reaction as well as separation by selectively removing a product in a continuous flow reactor; (6) Accomplishing simultaneous chiral production and separation in a bioreactor composed of lipase beads modified with chiral specific ligand(s). Candida antarctica lipase B (CALB) will be immobilized onto nanopore silica-chitosan composite for possible productions, in replacements of traditional productions using sophisticated synthesis and separation schemes, of fine chemicals to be used by pharmaceutical, food/nutrition, LCD industries. ? ? ?
