离子液体双液相甾体生物催化体系构建研究

项目名称： 离子液体双液相甾体生物催化体系构建研究

项目编号： No.21206127

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 化学工程及工业化学

项目作者： 毛淑红

作者单位： 天津科技大学

项目金额： 27万元

中文摘要： 甾体化合物在水中溶解度极低，严重影响甾体转化反应的速度和产率，成为甾体生物催化工业中亟待解决的瓶颈问题；传统双液相体系设计用于全细胞生物催化，可解决底物和产物在水相中溶解度低的问题，但对细胞具有毒性且污染严重。非水溶性离子液体具有较高分配系数及绿色环保等优点，成为替代有机溶剂构建双液相体系最有前途的分配相。本项目以雷斯青霉生物催化左旋乙基甾烯双酮15α羟基化为研究模型，根据定量构效筛选方法（QSAR），结合代谢活力及分配系数等，构建离子液体定量筛选模型，高效筛选具有高分配系数、低毒性的离子液体，建立两液相生物催化体系，同时利用雷斯青霉离子液体耐受菌株，高效生产15α羟基化左旋乙基甾烯双酮。本项目通过对离子液体定量筛选模型构建，离子液体双液相生物催化反应规律及菌体对离子液体耐受机理研究，为构建离子液体双液相体系应用于甾体生物催化提供理论基础，对实现甾体生物催化产业的技术升级具有重要意义。

中文关键词： 离子液体；甾体药物；生物催化；双液相；羟基化

英文摘要： Low solubility of steroids in aqueous media considerably limits the productivity of the biotransformation system, which has been a bottle-neck in steroid bitransformation. Biphasic processes are usually applied in the whole-cell biotransformation to overcome low water solubility of substrate and/or product and their inhibitory effect of substrate and/or product on the biocatalyst. Furthermore, commonly used conventional organic solvents often damage the microbial cells. Ionic liquids (ILs) were recommended as promising alternatives to organic solvents in two-phase bioreactive systems, as they are environment friendly and can dissolve a wide range of chemical compounds. In this research project, we will construct new quantitative screening model, based on 15α hydroxylation of 13-ethyl-gon-4-en-3,17-dione by P. raistrickii, to evaluate the applicability of ILs for biphasic system according to the quantitative structure-toxicity relationship (QSAR), in which the distribution coefficient of substrate and product, as well as metabolic activity of P. raistrickii, is considered. The selected ILs, with higher distribution coefficients and lower toxicity to microorganism, are used to construct two-phase system for the production of 15α hydroxylation of 13-ethyl-gon-4-en-3,17-dione by IL-tolerant P. raistrickii. Through t

英文关键词： Ionic liquids；stroids；biotransformation；biphasic system；hydroxylation