Combinatorial biosynthesis is the directional transformation and arrangement of biosynthetic gene clusters of microbial secondary metabolites through modern biological and chemical technologies, and produce a series of novel metabolites in homologous or heterologous host systems, followed by optimizing these metabolites through modification outside the host system to obtain more active compounds with special functions. The main steps include: 1) to study the biosynthesis mechanism of the target compound; 2) to design the molecular structure of the target drug with high druggability; 3) directionally transformation of gene clusters and host systems related to biosynthesis.

This technology has many advantages, such as: 1) it can improve the structure of the target compound to lower the toxicity, improve the pharmacokinetic properties, enhance the biological activity, and increase the druggability; 2) it can obtain efficient genetically modified engineered strains, and achieve large-scale production of target products.

The production level of microbial fermentation mainly depends on the genetic characteristics and culture conditions of the strains themselves. Normally, the low production capacity of genetically engineered strains is the bottleneck restricting their industrialization. Our microbial fermentation production platform is based on the research of synthetic biological mechanism and the analysis of bacterial growth dynamic curve. By adding metabolite precursors and optimizing CQAs of fermentation process, the fermentation precursors are effectively diverted to the target products and the production capacity of bacterial strains is improved. In addition, we further improve the production efficiency of strain fermentation by developing batch feeding fermentation process to extend the culture time and adopting solid phase adsorption process to avoid feedback inhibition in the fermentation process.

Through the microbial fermentation production platform, we have successfully overcome the technical difficulties from lab to industrial production, and can achieve stable and efficient production of commercial and pipelines products. The company's facility has passed the GMP compliance inspection in 2020, and is designed to meet the US and EU GMP standards.

This platform covers the preparation technology of oral dosage forms and injection forms (including nano formulation and freeze-dried powder), and is committed to improving the druggability of microbial small molecule compounds through formulation methods, and realizing the development and upgrading of microbial drug dosage forms. Based on such platform, we currently have several new formulation pipelines under development, including utidelone capsules (UTD2), utidelone nano particles, and BG22 particles, which are expected to meet unmet medical needs.