WHO data shows that there were about 207 million malaria cases in 2012, resulting in 627,000 deaths. Artemisinin drugs are currently the front-line drugs for the treatment of malaria. They are one of the few new drugs independently developed and internationally recognized by my country. At the same time, my country is also The largest producer of artemisinin raw materials. The artemisinin produced in my country is extracted from the plant Artemisia annua. However, due to the low artemisinin content in Artemisia annua and the unstable supply, the price of artemisinin bulk drugs fluctuates greatly, affecting the terminal preparations. Stable supply. The newly developed foreign technology to use biosynthetic technology to produce artemisinin in yeast and then semi-synthesize artemisinin has entered the industrialization stage. my country's status as the original researcher and main producer of artemisinin is seriously threatened.
This project belongs to the field of agriculture and biomedicine. It has been continuously supported by the national "Eleventh Five-Year Plan" and "Twelfth Five-Year Plan"863 key projects, as well as key projects of the Shanghai City Science and Technology Commission. It has applied metabolic engineering breeding technology to obtain high-content Artemisia annua strains, and developed comprehensive technical systems such as increasing leaf fertilizer production, saline-alkali soil planting, straw reuse and new uses of artemisinin. The formed patent technology network covers breeding from Artemisia annua annua annua (Metabolic engineering breeding patents cover single-gene transformation, multi-gene co-transformation, branch inhibition, transcription regulation, indirect regulation, glandular hair-specific promoter), planting (saline-alkali soil planting, foliar fertilizer), product development (straw reuse, new use of artemisinin) The entire industrial chain can achieve stable and low-cost supply of artemisinin and ensure my country's dominant position in this field. The main technical inventions are as follows:
Invention 1: Using metabolic engineering breeding technology to obtain multiple genetically modified Artemisia annua strains, the strain with the highest artemisinin content can reach 3.1%. In this technical system, we have obtained a series of patent authorizations, forming a complete patent technology network covering overexpression of key enzymes in artemisinin synthesis, blocking of metabolic branches, overexpression of indirect regulatory factors, transcription regulation, and glandular hair-specific promoters in main synthetic organs. The application of this technical system can make the production cost of artemisinin much lower than that of foreign yeast technology.
Invention 2: Based on the plant metabolic control strategy, the Artemisia annua foliar fertilizer technical system was invented. Stimulating factors such as salt solution or abscisic acid are sprayed before harvesting Artemisia annua, which promotes the rapid synthesis of artemisinin in a short period of time, which can be used in the original Artemisinin content is increased by 10%More than 30%, reducing the production cost of artemisinin by 10About 30%, which is lower than the cost of using yeast to produce artemisinin abroad.
Invention 3: A high-yield and high-quality planting technical system for Artemisia annua in saline-alkali land has been established, making it possible to mechanically plant Artemisia annua on abandoned saline-alkali land; a technology for using Artemisia annua stalk to produce functional wood-plastic materials has been invented, which solves the problem caused by a large amount of discarded straw during the planting of Artemisia annua., and adds additional economic benefits; New uses of artemisinin drugs for treating hyperlipidemia have been developed, the application scope of artemisinin drugs has been expanded, and the upstream planting and extraction industry has been driven by increasing market demand.
This project has obtained 16 national invention patent authorizations, applied for 2 PCT international patents, applied for 1 US patent, and applied for 15 national invention patents. He published 34 articles, of which 22 were included in SCI, and the paper was cited 212 times in total. The highest citation frequency of a single article was 67 times. It was the first in the world to obtain the "environmental release" certificate of genetically modified Artemisia annua, and completed the safety evaluation and biological function evaluation of the "environmental release". The patented foliar fertilizer technology has been applied and promoted in more than 20,000 acres in Chongqing, Hunan and Guizhou, the Artemisia annua producing areas, increasing economic benefits by more than 24 million yuan. These research and inventions can ensure my country's leading edge in artemisinin cultivation, production and research and development, and provide stable, high-quality and low-cost artemisinin bulk drugs to hundreds of millions of malaria patients around the world.