生物催化作为前沿的热点交叉学科，是国内外重要的科技创新和产业战略方向之一。异胡豆苷合成酶（STR）是单萜吲哚类生物碱生物合成的门控酶，但其生物催化应用基础研究才刚刚起步。课题组前期对STR结构生物学和化学生物学进行了深入研究，在此基础上,我们结合化学、生物学、计算等多个学科，设计并研究三类新底物的手性P-S催化，同时探索STR在手性催化三分子Ugi反应中的应用。本项目还将通过酶与反应底物和产物复合物晶体衍射分析，借助计算机辅助对接和点突变的方式，对STR手性催化这两类反应的机制进行系统研究，重点关注STR手性催化三分子Ugi反应的机制。通过本项目的实施，我们期望能进一步推进STR作为生物催化剂的应用基础研究。

As the forefront of interdisciplinary research, biocatalysis is now treated to be important strategic direction of both science and industry in many countries. Strictosidine synthase (STR) is the key enzyme of monoterpenoid indole alkaloid biosynthesis. But its biocatalytic applications remain unexploited for many years and has just arisen. Based on STR structure and early biochemical results, we will design three novel types of STR substrates for asymmetric Pictet-Spengler (PS) reactions and promote applications in STR based chiral catalysis of three-component Ugi reactions. Meanwhile, the catalytic mechanisms of these reactions, particularly the chiral 3-component reaction, will be disclosed by X-ray crystal structure of STR in complex with both the substrate and the product as well as computer-assisted docking and site-directed mutagenesis. The proposal herein combines chemistry, biology, computing and other disciplines. Through the implementation of this project, we hope to further promote the application and basic research of STR as biocatalyst.