Nanopore Enhanced Lipase Bioreactors

描述（由申请人提供）：该项目的主要目标是开发一种平台技术，纳米孔增强酶装置（NEED），用于生产对映体纯（即手性特异性）药物中间体。酶将被固定在纳米孔载体上，其孔形态和表面修饰将被专门设计，以进一步提高酶的活性和选择性。该项目的具体目标是：a .1以纳米孔二氧化硅-壳聚糖复合材料作为生物反应器固定化脂肪酶a .2通过修饰纳米孔载体和控制水活度来提高酶的性能a .3在NEED中实现协同反应和分离根据上述三个具体目标，我们建议在项目过程中完成以下技术里程碑：(1)将脂肪酶固定在二氧化硅-壳聚糖纳米孔复合材料上，同时保持其活性和选择性；(2)通过工程孔结构在纳米复合材料中形成开放通道结构和高比表面积，显著提高附着脂肪酶的反应速率；(3)通过在复合材料中加入表面修饰配体，增加亲疏水界面面积，进一步提高脂肪酶的活性；(4)利用壳聚糖相的溶胀率控制和微调脂肪酶周围的水活度；(5)在连续流反应器中选择性去除产物，提高反应效率和分离效率；(6)在由手性特异性配体修饰的脂肪酶微球组成的生物反应器中实现同时手性生产和分离。将南极念珠菌脂肪酶B （CALB）固定在纳米孔二氧化硅-壳聚糖复合材料上，以取代传统的复杂合成和分离方案，用于制药、食品/营养、液晶显示器等行业的精细化学品生产。

DESCRIPTION (provided by applicant): 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.