This project belongs to the field of biology and medicine technology. The key to the escalation of the Sino-US trade war is the United States 'desire to comprehensively curb the rise of China! China has become the world's largest manufacturing country since 2010. However, a huge technical bottleneck in the development of my country's biotechnology industry is the mismatch between upstream strains and downstream fermentation projects, and the lack of original innovation in the discovery of new natural drugs in China has seriously restricted my country's transformation and upgrading from a manufacturing country to a manufacturing country The project focuses on theoretical innovations and technical methods for efficiently discovering and intelligently manufacturing novel mechanism natural products. It uses the independently constructed microbial strain library and natural product library, and uses a technical platform of high-throughput natural product weight removal and interactive activity screening to efficiently discover and Identify and analyze the biosynthetic mechanisms and mechanisms of action of novel active natural products; Combine the efficient biosynthesis of upstream active natural products with downstream biochemical engineering, realize big data and intelligent research on product production, and form a complete research system for microbial drug research and intelligent manufacturing&&: 10,000 Actinomyces library and GNPS technology platform for efficient screening of novel active natural products: created the largest and highest-quality microbial strain library built by a single laboratory, and discovered dozens of new genera and new species; Innovatively establish a high-throughput secondary mass spectrometry small molecule network weight removal system, and efficiently discover active natural products with unique structures and novel molecular mechanisms of action in this microbial strain library, such as deepmarycin J with anti-TB activity. Five of them were rated as& ldquo;hot molecule& rdquo; by NPR, laying the theoretical and material foundation for subsequent drug discovery of natural products. Based on the unique mechanism of drug synergy, a new technology for high-throughput interactive activity screening has been established: the concept of high-throughput ldquo; interactive activity screening rdquo; was proposed for the first time, and the candidate drug Beauveria bassiana was successfully obtained. Preclinical experiments have been completed to clarify the mechanism of action. It was found for the first time that the combination of avermectin and ketoconazole had a new synergistic antifungal effect. This technology has become a powerful tool for interactive drug combination discovery and has been commented by the NCB as an ideal opportunity to decipher the targets of antifungal drugs. Combine the efficient biosynthesis of important active natural products with biochemical engineering, explore theories, methods and key technologies, and realize scale-up production in microbial cell factories: establish core technologies such as biocatalyst molecular design, pathway reconstruction, and global optimization and regulation, and Conduct quantitative prediction of Streptomyces, laying an important foundation for applying synthetic biology concepts to transform natural products and activate silent gene clusters; The high-yield mechanism of avermectin and erythromycin was analyzed, and the multi-scale theory of biological processes was realized in a bioreactor combined with biochemical engineering, combining product big data with intelligent research. Jay D., American Academy of Engineering. Academician Keasling and Academician Deng Zixin of China Academy of Sciences highly affirmed this. Representative achievements of this project include 7 SCI papers (he cited 318 times, including 3 papers on PNAS and 1 paper on Angew Chem Int Ed) and 1 academic monograph in English (both downloads and circulation exceeded 10,000 times). He has published more than 100 papers, cited a total of 4000 times, authorized 10 invention patents, and focused on the transformation and application of natural products, such as avermectin and erythromycin. The first person to complete this project serves as editor-in-chief of Syn Sys Biotech and deputy editor-in-chief of AMB. A total of 30 doctoral/master's degree students have been trained (1 person won the Outstanding Doctoral Thesis Award of the Chinese Academy of Sciences) and 12 postdoctoral students have been trained. 1 person was awarded the chairmanship of ICBS and re-elected (2016 - 2018), 1 national outstanding young person, ldquo; New Century Ten Million Talent Project rdquo; 1 national candidate, 1 chief scientist of the 973 project, 1 Chinese Academy of Sciences;1 person, 2 experts in the field of the 863 project, and 1 person with the WuXi AppTec Life Chemistry Award.