In 2021, the synthetic biology climbed to the top of its development so far. According to a report released by Synbiobeta, an American synthetic biology media, start-ups are crazy in raising money, with an overall investment of nearly $18 billion.
Synthetic biology companies can be divided into two categories according to their layouts of industrial chain: whole industry chain companies and platform companies. The latter focuses on services and provides customers with technical support of synthetic biology, including representative enterprises such as Ginkgo and Zymergen. Whole industry chain companies have both synthetic biology technology and market-oriented products. Among the nearly $18 billion investment in 2021, the financing of "application" categories (such as food, medicine and chemicals, etc.) accounted for about 75%, and the financing of "bioengineering platform" accounted for about 15%.
"The large-scale capital shot began in the middle of last year, while it was mostly in the warm-up stage of keen attention before that." Zhiqian Zhang , the founder and CEO of Tidetron, said in an interview.
Founded in 2021, Tidetron is a whole industrial chain company and has taken the lead in realizing the mass production of 30 kinds of synthetic biological products such as peptides and erythritol under the leadership of its founder. Within 10 months after its establishment, the company received four rounds of financing, which came from Unity Ventures, ZhenFund, Legend Capital, IDG Capital and other investment institutions. The total financing amount is over $100 million. The latest round of financing will be mainly used for R&D and production of new lines, including R&D and mass production of new commodity materials, pharmaceutical intermediates and mass production. At present, the company is in a silent period of financing, but Mr. Zhang said that he welcomes in-depth cooperation between academic circles and industries at any time.
"In terms of financing, every investment institution will have its own consideration. Our company has gained much recognition and completed four rounds of financing in a short time. On the one hand, Tidetron is the first company that practically solves the problem of changing a laboratory into a factory, and we have realized the mass production of various substances; On the other hand, it is also the reason for the overall trend in the field. "Mr. Zhang said. It is understood that Tidetron is the one of the first bio-manufacturing platforms to realize multi-substances mass production in China.
This time, SciPhi SynBio invited Zhiqian Zhang , the founder of Tidetron, to have interview and share the company's development history and future plans with us.
Unique Strain Library, Basic Component Library and Microfluidic Platform
Zhigan Zhang, a Generation Z, studied clinical medicine at Zhongshan School of Medicine, SYSU. Early in the university, he learned about synthetic biology and viewed it as his development goal. He participated in iGEM (International Genetically Engineered Machine Competition) and won the gold medal and the Best Therapeutics Project. He also visited Yale University. Attracted by the prospect of "synthesizing substances on demands", he also found the problem of "mass production" to be solved.
In 2017, he build a laboratory with other partners who were also fond of synthetic biology, and this is the initial core team of Tidetron. The small world is pregnant with their big dream, that is, through the transformation of microorganism, scientific research achievements could be applied in industrialization from laboratory and the transformation of production could be completed.
The team first set out to build a technical platform, including the strain library, the basic underlying component library and a high-throughput screening platform. In the early stage, they devoted themselves to research for many years. When the technology gradually became mature, they began to produce and test some substances. Then, they made adjustments and transformation on strains according to the results.
According to Zhiqian Zhang , a variety of mainstream gene editing tools are used to transform strains. Taking CRISPR-Cas system as an example, it has the functions of "positioning" and "editing": CRISPR is equivalent to "GPS positioning system", and Cas series proteins are scalpels of DNA. Through these tools, the target gene is inserted into the chassis strain, and random mutation is introduced by directional evolution, so as to make as many samples of engineering bacteria as possible. The number of cells is usually 1010-20, which greatly improves the success rate of R&D.10-20
Then, the advantageous mutation, that is, the dominant strain, is screened out from the massive sample database. This is also an important step limiting speed in the whole R&D chain. Therefore, it is necessary to have a high-throughput screening platform. The flux of microfluidic platform of Tidetron can reach 10^9, 3-4 orders of magnitude faster than that of traditional screening methods (10^5-6).9It shortens the screening time of strains from several years to several months and greatly accelerates R&D speed.5-6
After the best strains are screened out at a high speed by microfluidic platform, they will be fermented rapidly in the intelligent fermenter customized by Tidetron.
“At the end of 2020, we finally completed the verification and transformation of research and development. We constructed our component library through various gene editing tools, directional evolution and microfluidic platform. We built a Tidetron Altra platform-based strain library with mass production capacity and universality. With the help of our unique technology from the platform and aggregated scientific research strength, we not only have scientific research services, but also welcome to share the platform with academic circles and industries.” said Mr. Zhang . Tidetron has successively carried out joint research and practical cooperation with scientific research units such as Sun Yat-sen University, Jiangnan University, and the Key Laboratory of Materials Chemical Engineering, etc.
Further Broaden the Product Layout
Mr.Zhang said to SciPhi, “Recall our star-up, we only got millions of angel financing, so the top priority was surviving.”
“In terms of product layout, the team first selected products with short R&D period and low risk for test. We finally selected peptides, because it did not consume too many raw materials and the production schedule was relatively loose.”
In fact, as Zhiqian Zhang expected, the mass production of products had a good start. At present, Tidetron is involved in consumer goods such as cosmetics, food and beverage, household cleaning, etc. Tidetron has more than 20 kinds of peptides, food sugar substitute erythritol and other products, and more than 30 kinds of substances on sale with the annual output of the factory exceeding 10,000 tons.
According to Zhiqian Zhang , the income of Tidetron in 2021 is nearly 100 million yuan. When talking about the reasons why their products are favored by consumers, he explained, "Compared with similar biosynthetic products, our products have the advantages of high purity, stable quality, good activity and safety. In terms of strains and technologies, the fermentation strains designed by genetic engineering have strong universality, rapid reproduction iteration and higher production efficiency than traditional strains."
In terms of environmental protection, the principle of Tidetron is "It’s growing". It pays special attention to the discharge of "three wastes" (including waste gas, waste water and solid waste) in the production process. Compared with chemical synthesis, biosynthesis production greatly reduces environmental pollution. "According to the previous tests of Tidetron, as far as peptide products are concerned, pollution emissions can be reduced by more than 95%."
Based on the current good business situation and transformation experience, Tidetron has begun to broaden its product layout. Mr. Zhang said that they will make internal and external evaluation in choosing products, taking strength, pace, market and value of products, etc into consideration. At present, they have entered the food field. In the next year or two, they will choose two or three key areas to focus on, including bulk materials and medicine, They will work hard and steadfastly according to a certain pace. However, at present, there will be a long way to go to make biosynthetic substances replace chemical industry as the mainstream production mode. The market is as huge and the challenges.