药用植物是天然产物的最大资源王国，天然产物单体的分离或制备是新药开发的关键。药用植物中有效组分含量低、分子结构复杂，给天然产物单体的分离或合成带来了很大的难度。虽然合成生物学的发展给天然产物合成迎来了新突破，然而植物来源的酶在工程菌中活力低、重构的植物酶的顺序协作催化效率低等因素导致难以获得足够量的天然产物进行较深入的药理活性研究。本研究利用植物界丰富的天然产物合成酶的生物学信息，跨界进化分析获得微生物源的同工酶，重点进行藏红花、人参及红景天等植物的相关糖基转移酶序列与特征模序的进化分析，解析酶底物结合域残基，跨界理性筛选微生物来源的具有相似功能的糖基转移酶。利用微生物酶的高合成催化活性与易改造的特性，显著提高合成效率，实现多位点高选择性催化与反应高效调控。同时，提出跨界基因探矿的分子机理，为其它天然产物合成酶类的跨界基因数据挖掘提供重要参考。

Chinese herb is the largest resource of natural products. The separation and preparation of monomer natural products plays an important role in the exploitation of new drugs. However, the low content of the substances and large amount of analogs exist in corresponding plants, which make the preparation of adequately pharmaceutical pure compounds difficult in large amount. On the other hand, the complexity of structure of natural products also creates more obstacles to synthesis. Although synthetic biology provides a significant driving force to develop the synthesis of natural products by assembling biosynthetic pathways and heterologous expression, the low activity and efficiency of these enzymes in catalyzing sequential reactions still make it difficult to obtain sufficient natural products for deeply pharmacological activity research. Recently, with a large number of bioinformatics shared in the data base, the increasing massive information of enzymes involved in the synthesis of secondary metabolites makes it possible for us to mine isoenzymes bestriding plant kingdom. In this study, by analyzing key residues for substrate recognition and evolution of the distinct motif of glycosyltransferases related to biosynthesis of some important natural glycosides, several microbe isoenzymes could be rationally mined and were mainly used to solve the problems in the synthesis of crocin, salidroside and ginsenoside. Then, we will propose the mechanism of glycosyltransferase of glycosides synthesis. In virtue of higher catalytic activity and engineered genetically tractability of microbe enzymes, the highly efficient catalysis and regioselectivity regulated biosynthesis of target important natural glycosides could be achieved. Meanwhlie, the mechanism of microbe genome mining bestriding plant kingdom for synthesis of the natural glycosides would be provided an important reference for mining other functional enzymes.