围绕丹参等中药资源品质问题：①首次克隆鉴定了丹参酮生物合成关键酶基因SmDXS，SmHMGR和SmGGPPS等，并用大肠杆菌颜色互补法，建立了丹参等中药萜类成分合成相关基因的功能解析平台；②用“发根诱导差异筛选”策略，明确了丹参酮生物合成调控的关键靶点基因，并首次用转基因技术证实丹参酮合成依赖于MEP途径，揭示了丹参有效成分的累积机制；③开发“代谢工程与诱导子处理耦联”和“量子点调控”等策略，有效提高了丹参中活性成分的产量，还深入解析了中药多酚类有效成分与体内血液载体蛋白的互作规律，提供了良好借鉴。最近在Metab Eng（IF=8.26）等发表SCI论文60余篇（SCI他引600多次，单篇最高32次，H-index为19）；国家发明专利授权14项；获2009年上海青年启明星（跟踪）和2013年教育部新世纪人才等人才计划；2014年明治生命科学奖，2015年上海中医药科技三等奖（排名1）。

The applicant’s works focused on quality improvement of Traditional Chinese Medicines (TCMs). (1) Some key tanshinones biosynthetic genes such as SmDXS, SmHMGR and SmGGPPS were firstly isolated from Salvia miltiorrhiza, while the color complement strategy in E.coli was developed to identify the function of genes involved in terpenoid biosynthetic pathway in a quick and convenient way. (2) Differential screening strategy of elicited hairy roots was successfully developed to screen key regulation target genes from many candidate genes involved in tanshinones biosynthetic pathway, and biosynthesis of tanshinones were firstly confirmed to be mainly derived from MEP pathway by transgenic experiments, providing useful information to further understand molecular mechanism. (3) The “metabolic engineering coupled with elicitation” and “Cd-Se QDs regulation” strategies were firstly established to enhance the accumulation of active constituents in TCMs, while active polyphenolic compounds from TCM was comprehensively investigated for their interaction mechanism with blood vector proteins as well as constructed new bioactivity evaluation method for obtained biotechnological materials, which provided good references for other medicinal compounds in TCMs. The applicant has published 66 peer-review SCI articles in international journals such as Metabolic Engineering（IF=8.2），Scientific Reports (IF=5.1), Nanomedicine (IF=6.7) and Integrative Biology (IF=4.5) etc. These publications have obtained more than 600 citation times by other researchers with the highest citation of 32 for one article. 14 Chinese invention patents were authorized as the first inventor. The applicant received Meiji Dairies Life Science Award in 2014, the Third Prize of Shanghai TCMs Science and Technology (ranked the 1st) and the Second Prize of Shanghai Teaching Achievement in 2014 (ranked the 5th). The applicant was selected as excellent scholars in the “Program for Shanghai Tracking Rising Star of Science and Technology in 2009” and “Program for National New Century Excellent Talents in University of 2013” etc.

本项目以系统生物学的手段，通过比较转录组、代谢组和蛋白组将道地药材的表型、遗传与环境研究有机结合，阐释了道地药材复杂表型变异的遗传机制。取得创新性结果包括：（1）道地药材形成的分子机制：首先以道地药材丹参为模式药材，克隆鉴定了丹参酮生物合成途径中二萜合酶和下游P450基因；发现丹参有4条二萜代谢途径，明确SmCPS1是丹参根部参与丹参酮生物合成唯一起始环化基因；在验证CYP76AH1催化次丹参酮二烯生成铁锈醇的基础上，进一步发现CYP76AH3、CYP76AK1连续催化铁锈醇形成11，20-二羟基铁锈醇和11，20-二羟基柳杉酚，并实现了合成生物学生产，进一步解析了丹参酮下游合成途径，深入揭示了丹参二萜有效成分形成的分子机制。此外，克隆鉴定了雷公藤、冬凌草、穿心莲、黄芩、金银花等道地药材次生代谢相关基因，从基因水平阐释其有效成分形成的分子机制。（2）道地药材代谢特征成分分析：开展了罗汉果、天麻、重楼、枸杞和苍术等道地药材代谢特征成分分析。从罗汉果中鉴定出53个黄酮醇和黄酮苷类、59个三萜皂苷和10个罗汉果酸苷成分。在天麻中发现了152个化合物，其中70个首次报道。建立了同时测定8种重楼皂苷的分析方法，对15种重楼属植物中重楼皂苷进行了评价。建立了枸杞果实中甜味成分的测定方法，考证并确定了宁夏枸杞道地性。以苍术为例，通过最大信息熵模型、相关分析和地理信息技术研究揭示中药材品质（指标特征成分）与生态适宜度之间的关系，解释中药材道地性。（3） 道地药材的分子鉴别：构建了滇皖产区铁皮石斛居群SSR分子身份证，为铁皮石斛的品种鉴别提供准确方法。采用多重位点特异性PCR鉴定了霍山石斛、铁皮石斛与齿瓣石斛药材；并对金银花基原植物及配方颗粒进行了有效鉴定。首次采用高分辨率熔解曲线分析鉴别了商品石斛和西红花药材的真伪。（4）药用植物新种发现：①安徽省景天属一新种：旋枝景天；②广西省栝楼属一新种：那坡栝楼；③西藏茄科枸杞属一新种：苦枸杞。研究结果对于道地药材的品种选育、分子鉴别及资源可持续利用具有重要指导意义。共发表论文79篇，其中SCI收录33篇，累计影响因子102；获得中国药学会科技奖一等奖1项和发明专利10项，主编专著《分子生药学(第三版)》获得第四届中国出版政府奖；项目负责人2015年当选中国工程院院士。