微生物全细胞催化黄酮类化合物酰化修饰及其影响机理研究

黄酮类化合物是一类具有独特化学结构和药理活性的天然多羟基化合物，其经选择性酰化修饰后可获得理化性质改善、抗癌活性增强且具有良好生物相容性的酯类衍生物，应用潜力极大。本项目基于天然产物来源的抗癌新药研发的迫切需求，针对目前黄酮结构修饰中化学法和酶法修饰技术存在的不足，拟以黄酮类酯类化合物合成为目标，采用微生物细胞为新型绿色催化剂，探讨黄酮类化合物的区域选择性酰化修饰，揭示培养要素对全细胞联接酶的诱导/阻遏表达调控及催化活性调控关系，阐明反应介质因素对全细胞催化黄酮类化合物区域选择性修饰、催化剂稳定性的影响机理及全细胞催化剂在反应中的底物识别机理，实现全细胞催化技术在黄酮类化合物结构修饰过程中关键科学问题的认识突破；在此基础上构建具有较高应用潜力的绿色全细胞催化体系，用于替代化学法和酶法、提高过程经济性，为推动全细胞催化技术在我国医药、化工、食品及相关新兴产业中的应用突破提供理论支持。

Flavonoids are kinds of natural polyhydroxyl compounds with special stereostructure and multiple bioactivity. Regioselective acylation of flavonoids can led to new compounds with significantly improvement in both physiochemical properties and anticancer activity, which made this field even more promising and have attracted much more attentions. Considering the urgent need of low side-effect anticancer agents from natural sources, basic researches on whole cell biocatalysis will be explored for regioselective modification of flavoids. The Relationship between the crucial environmental factors (including cultivation and the reaction conditions) and the biosyntheisis/catalytic performance of whole-cell biocatalyst will be originally investigated in acylation of flavonoids. By investigating influence of substrate structures on the catalytic performance of the whole-cells, the substrate recognition mechanism of whole cells and its enzyme molecular basis in acylation of flavonoids will be revealed for the first time. The researches will be helpful in achieving a breakthrough in the catalytic mechanism of whole-cell catalyzed modification of poly-hydroxyl compounds by regioselective acylation. Based on the above-mentioned research work, a novel, cost-attractive and highly efficient whole-cell biocatalysis system will be build for modification of flavonoids, instead of traditional chemical method or the enzymatic method for improving the process economy, reducing the material consumption and energy consumption in the modification process, and providing theoretical references to made a breakthrough in application of whole-cell biocatalysts in medicine industries, chemical industry and other industries in our country.