This project belongs to applied basic research in the field of traditional Chinese medicine resources science.
Innovation in Chinese herbal medicine biotechnology is the driving force for the sustainable development of the Chinese medicine industry. The team of project completers has long been engaged in biotechnology research on traditional Chinese medicine resources. In view of the problems of low active ingredient content, serious quality degradation, unclear synthesis control mechanism, and unclear interaction mechanism between active ingredients and proteins in the body, tanshinone, hyoscine and food-derived polyphenols are the main research objects, and research work is carried out from the aspects of metabolic regulation of active ingredients, quality improvement of Chinese medicinal materials, biosynthesis of active ingredients and mechanism of action in vivo. The remarkable results achieved are summarized as follows:
1)Genes related to tanshinone metabolism and synthesis, such as HMGR, DXS and GGPPS, were first cloned from salvia miltiorrhiza. The dependence relationship between the expression of 12 related genes and tanshinone accumulation was analyzed, and the molecular mechanism of four induction treatments promoting tanshinone synthesis and accumulation was explained;
2)For the first time in the world, transgenic technology has been used to confirm that tanshinone synthesis depends on the MEP pathway, and the gene co-transformation strategy has been used to increase the tanshinone content in the roots of transgenic salvia miltiorrhiza by 4.7 times;
3)Five tropane alkaloid metabolic synthesis genes were cloned from Sanshenshan, and for the first time, TRI was combined with PMT or H6H to transform Sanshenshan, which significantly promoted the accumulation of total tropane alkaloids in Sanshenshan;
4)A model suitable for studying the interaction between active ingredients of traditional Chinese medicine and blood carrier proteins was established. Multi-spectral characterization methods combined with quantitative structure-activity relationships were used to conduct in-depth research on the interaction rules of active ingredients and blood carrier proteins, and the food-derived polyphenol substances and blood carrier proteins were systematically explained. Interaction rules.
The above research results provide a good reference for analyzing the quality formation mechanism of Chinese herbal medicines, using biotechnology to obtain active ingredients of traditional Chinese medicines, and in-depth elucidation of the mechanism of action of Chinese herbal medicines in vivo and the development of new drugs and health products.
During the research period of this project (2007-2013), 68 SCI papers were published in internationally renowned journals such as "Metabolic Engineering"(IF=8.258) and "Critical Reviews in Food Science and Nutrition"(IF=5.548)(including 20 representative works, which have been cited 404 times by SCI and cited 277 times by others), and 12 national invention patents were authorized. Relevant academic achievements have received widespread attention and high praise from international colleagues. For example, European scholar Professor Pavlov wrote an article that spoke highly of our work "innovatively using genetic engineering and inducer technology to promote in-depth research on the secondary metabolic and synthetic mechanism of salvia miltiorrhiza" and "The push-pull strategy was used to effectively increase the content of tanshinone in salvia miltiorrhiza, and the functions of HMGR, GGPPS, and DXS and their importance in the synthesis of tanshinone were clarified." Applicants have been selected into the Ministry of Education's "New Century Outstanding Talent Support Plan"(2013), the Huo Yingdong Youth Fund Talent Plan (2012), and the Shanghai City Youth Science and Technology Star (Tracking) Talent Plan (2009) and other talent plans. Relevant scientific and technological achievements of this project have been successively applied by the Institute of Plant Physiology and Ecology of Shanghai Academy of Life Sciences, Chinese Academy of Sciences, School of Pharmacy of Soochow University, Jiangsu Province Key Laboratory of Medicinal Plant Biotechnology, Jiangxi Province Key Laboratory of Natural Product Development and Utilization, and Shaoxing City Research Center and other academic institutions or units, which have effectively promoted the scientific research progress of relevant units and produced extensive social benefits; Relevant scientific and technological achievements have also been applied by Shanghai Yusen New Drug Development Co., Ltd., Shanghai Tianniantang Health Technology Co., Ltd. and Shanghai Shangzong Traditional Chinese Medicine Technology Co., Ltd. in the preparation of tanshinone and other traditional Chinese medicine extracts and the research and development of related health products and drugs. Good social and economic benefits have good prospects for promotion and application.