Shenghui SynBio chatted with Dr. Li Ruifeng, CTO of Huili Biologics. Li Ruifeng has both a background in chemical and biological enzymology, and has rich practical experience in enzyme design and screening and industrial application process development, and has successfully commercialized a number of innovative biocatalysis technologies. (2017) The development of Huili Biologics stems from the development of a new technology in 7 and is also one of the core products of Huili Biologics (MPCA). The traditional chemical synthesis of pyrazinecarboxylic acid has low efficiency, many by-products, and high environmental pressure, and the oxidation of such chemical alleles is more suitable for biocatalysis. Based on this, Huili Biotech selects the biological enzymatic route for systematic design optimization, through the process of finding enzymes, optimizing enzymes and strain screening, reversely derives and refines different synthesis modules of pyrazinecarboxylic acid, and then applies the biosynthesis technology to each module, and finally forms an industrialization technology with high technical barriers, forming an alternative trend to the traditional process, and the current product is also in short supply. According to Li Ruifeng, the technology has been recognized by academia and industry. At the academic level, the technology is advanced and original; At the industrial level, after industrial processes such as pilot scale-up production and production line construction, the product is finally introduced to the market. "More importantly, we have a deep understanding of a new technology from concept to laboratory verification, to the real realization of mass production and landing to the creation of economic benefits, through the development of this project also opened up the commercial closed loop of product from laboratory research and development to market, cultivated a cross-background and capable team, and laid a good foundation for the development of subsequent projects." He added. In July this year, Huili Biotech announced the completion of a series A financing of nearly 3 million yuan, which was jointly led by Legend Capital and Boyuan Capital, and co-invested by Qianji Capital, Yunqi Capital and Zhongwei Capital. Speaking about financing, Li Ruifeng said, "We are very cautious and conservative in the assistance of introducing capital, and hope to be able to play steadily. After the mass production and profitability of pyrazine, the team accelerated the pace of research and development, accumulated some new projects, and very quickly entered the stage of small-scale, pilot, and even near-mass production. With the help of financing, the existing team, R&D platform can be greatly upgraded, and the commercialization of products that are already ready for mass production can be promoted. (10) The first computing platform in China to realize the full-scenario design of enzymes, as the saying goes, if you want to do things well, you must first sharpen your tools. Huili Biotech's core technology platform, enzyme calculation design platform, is a domestic computing platform to realize full-scenario design of enzymes. The R&D team has accumulated deep experience in the computational design and application of enzymes in industrialization, such as calculating the chirality obtained β-amino acid synthetase, which is designed by artificial intelligence to achieve industrial application standards Quasi-classic case. There are also some industrial enzymes with high stability design for industrial applications have been significantly improved, established a set of unique design methods and strategies as the core technology of enzyme design platform, Li Ruifeng introduced, Huili Biotech R&D Center's enzyme calculation design platform is still under construction and improvement, core enzyme calculation design platform construction includes a series of software package writing, design process combing optimization, etc.; More importantly, the company has built a team with cross-background and deep accumulation in enzymology, including experts in computational chemistry and industrial enzyme applications. In addition, Huili Biotech is also equipped with an enzyme design platform that can connect front-end design development and midstream and downstream development, test the performance of mutant enzymes and feedback to the experimental team of front-end design, and form an iterative optimization mode of data and algorithms. At present, based on the above platform, the company has transformed products in the pharmaceutical field, efficiently completed laboratory development, industrialization and production to commercialization, and deployed more than <> innovative products in multiple fields.

Talking about product research and development planning, Li Ruifeng said that it will first extend around the vertical upstream and downstream of existing products, such as several pharmaceutical intermediates, on the basis of achieving mass production or about to achieve mass production, layout the development and declaration of upstream raw material preparation technology and downstream API technology, open up the industrial chain from bulk cheap chemicals to APIs, and form a full range of multiple barriers such as core biological fermentation technology, key raw material production technology, complete industrial technology chain, and regulatory and policy access. Continue to strengthen the competitive advantage of existing products and eventually form a dominant monopoly market pattern; Secondly, focusing on several fields such as pharmaceutical intermediates, animal protection, and food, we will continue to horizontally expand specific product pipelines. In terms of product selection, Huili Biotech follows the following logical points: first, the market situation, whether it is needed by the market, the market has a gap or has future growth potential; Secondly, whether there is a bottleneck in technology, such as the construction of chiral centers in the structure, regional selective response, etc. "If these two basic conditions are met, the product market acceptance is faster and higher, and at the same time, high technical barriers and technical advantages can be formed, and the life cycle of product technology can be extended to the greatest extent."

Finally, Li Ruifeng also shared his views on the design and modification of enzymes in synthetic biology with SynBio. In his view, nature contains countless enzyme resources, with the rapid development of synthetic biotechnology, it has promoted the rapid accumulation of basic biological resources such as protein sequences, structural functions and catalytic mechanisms, and new biochemical synthesis pathways, which has greatly promoted the transformation of biological enzyme resources into industrial applications. From single-enzyme catalysis to multi-enzyme cascade, the regulation of biosynthetic pathways to the heterologous construction of new biochemical pathways, in essence, it is still the regulation and application of enzymes to achieve biocatalytic functions, in fact, natural enzymes are usually difficult to meet the needs of industrial applications and modify their performance Making or customizing some of these core catalytic enzymes became central to the development of a biocatalytic technology. Synthetic biology technology has not only pushed a new wave in the mining, preparation, application and other fields of enzymes, but also advanced the design and transformation of enzymes until the design of new artificial enzymes to a new era. On the other hand, the joint cooperation of perfect upstream, middle and downstream technology development platform, engineering equipment construction, application mining and other aspects is also a very important condition for promoting the rapid commercial landing of a biological enzyme technology.