离子液体溶剂中磁性固定化酶催化合成半合成抗生素和介质作用机制研究

项目名称： 离子液体溶剂中磁性固定化酶催化合成半合成抗生素和介质作用机制研究

项目编号： No.21663020

项目类型： 地区科学基金项目

立项/批准年度： 2017

项目学科： 环境科学、安全科学

项目作者： 薛屏

作者单位： 宁夏大学

项目金额： 20万元

中文摘要： 随着环境污染问题的日益加剧，发展从源头消除污染的绿色酶催化技术是我国-内酰胺类抗生素产业可持续发展的必然要求。本项目针对传统酶法制备半合成抗生素使用有机物介质严重存在着催化效率低、选择性低、原料利用率低和污染环境等问题，选择离子液体溶剂作反应介质，以易分离可循环使用的磁性高分子微球固定化青霉素G酰化酶催化合成阿莫西林、头孢羟氨苄和头孢克洛；基于离子液体组成与性能的可调控性，设计咪唑阳离子[(R1R2im)+]离子液体溶剂，在不同的离子溶剂调控水活度(aw)和pH值进行反应，探索离子液体溶剂的亲水性、疏水性和水活度等性质与酶催化性能之间的内在联系，反馈优化介质体系、磁性固定化酶和酶催化合成工艺，力求提高酶催化活性和选择性；通过对酶分子在离子液体溶剂中结构和酶学特征与酶催化活性及选择性的研究，揭示离子液体溶剂的介质作用机制，建立离子液体溶剂磁性固定化酶催化制备半合成抗生素的新绿色合成体系。

中文关键词： 离子液体；半合成抗生素；介质效应；磁性固定化酶；绿色合成

英文摘要： One of the main tendencies of sustainable development of the domestic -lactam antibiotics industry is to develop green enzymatic technology with the aim of eliminating pollution in the first place and the serious contaminated environment. Aiming at the limitation of the traditional enzymatic synthesis of semi-synthetic antibiotics in low yield, low selectivity, low utilization rate of substrates and environmental polluting due to large volume of organic solvent used, the ionic liquids-based solvent with adjustable properties and the immobilized penicillin G acylase(PGA) on porous magnetic micron-sized polimetic beans has been selected to synthesize amoxicillin, cefadroxil and cefaclor. The main problem in this project is regulating the imidazole [(R1R2im)+] ionic liquids-based solvents and carrying out the reaction in the solvent with different water activity (aw) and pH at different temperature to explore the relationship between the catalytic properties of the immobilized enzyme and the hydrophilicity, hydrophobicity and aw of the solvent. We will study the effects of the ionic liquids-based solvent on the structures and enzymatic properties of PGA, disclose the mechanism of the medium effects on the activity and selectivity of PGA and establish an efficient and green system for synthesizing semi-synthetic antibiotics.

英文关键词： ionic liquids;semi-synthetic antibiotics ; mechanism of medium effects;magnetic immobilized enzyme;green synthesis