Beyond Pharmaceuticals: Microcyto's Vision to Return Material Production to Nature

In recent years, the field of synthetic biology has witnessed leapfrog development, driven by the interdisciplinary integration and convergence of artificial intelligence with life science technologies such as metabolomics, transcriptomics, proteomics, gene editing, DNA assembly, and gene expression regulation.

Globally, the most well-known case in this field is DuPont’s successful conversion of glucose derived from widely available and low-cost corn hydrolysate into 1,3-propanediol (1,3-PDO) using microbial fermentation technology, thereby replacing chemical synthesis methods that entail high production costs and significant environmental pollution. This achievement demonstrated to the public the application potential of synthetic biology in biomanufacturing and is widely recognized as a paradigm for the industrialization of metabolites through genetic engineering approaches.

Among the innovation areas prioritized for national support, synthetic biology is a specialized field characterized by late deployment but rapid development.When it comes to synthetic biology, one institution that most people in China cannot overlook is the Institute of Microbiology, Chinese Academy of Sciences. If we trace the technological origins of domestic synthetic biology companies, we will find that the majority of them stem from the Institute of Microbiology, Chinese Academy of Sciences.

MicroCyto is precisely such a synthetic biology company, founded by Dr. Liu Bo in late 2021.

Dr. Liu Bo, the founder, graduated from the Institute of Microbiology, Chinese Academy of Sciences. He studied under renowned scientists in the fields of synthetic biology and microbiology, such as Tao Yong, and has accumulated nearly a decade of research and industrial experience in synthetic biology.“In recent years, many investment institutions have consulted me on synthetic biology. Through conversations with investors, I realized that publishing academic papers and developing industrial applications are two entirely different endeavors; technology can only maximize its value when applied to industry. I have also clearly sensed a fundamental shift in China’s entrepreneurial landscape, with an increasing number of scientists personally engaging in entrepreneurship.”

During his research tenure at the Institute of Microbiology, Chinese Academy of Sciences (CAS), Dr. Liu Bo was awarded the “Special Funding” under the CAS’s inaugural Special Research Assistant Program. As a key member of the research team, he participated in more than ten major national projects, including the National Key R&D Programs, the National Key Special Project on Synthetic Biology, the 973 Program, the National Natural Science Foundation projects, and key strategic initiatives deployed by the CAS. He has successfully developed multiple technologies that have been transferred to enterprises.

When facilitating project commercialization at the Chinese Academy of Sciences, Dr. Liu Bo’s greatest impression was:Core technical personnel had clearly successfully transferred the technology and processes to the company in the early stages, yet production issues would arise as soon as these personnel departed.

“We have reviewed this phenomenon multiple times. Ultimately, we discovered that,”“Every stage of the biomanufacturing process, including upstream strain development and downstream production technology development, involves substantial industry know-how. These aspects require scientists’ direct guidance or participation to accelerate project progress, which is another major reason why I chose to personally engage in entrepreneurship.”Dr. Liu Bo told VCBeat.

In addition to the founder’s extensive research and industry experience in synthetic biology, MicroCyto’s other core team members hail from the Institute of Microbiology of the Chinese Academy of Sciences, Tsinghua University, Sichuan University, Finnish national research institutions, and leading traditional biomanufacturing companies. With an average of over six years of experience in synthetic biology R&D, the team has developed more than 30 internationally leading technologies, which have been successfully commercialized through partnerships.

It is worth emphasizing that this October, after retiring from the Institute of Microbiology, Professor Tao Yong chose to officially join the startup MicroCyto as Chief Scientist, further strengthening MicroCyto’s team capabilities.

Excellent teams naturally attract the favor of capital.Despite the sluggish capital environment, MicroCyto completed two rounds of financing this year:In June this year, MicroCyto closed a RMB 100 million Pre-A financing round, led by Beijing State-owned Capital Management Shunxi Fund, with participation from Beidaihe New Area High-Tech Industry Fund and Henan Investment Group Huirong Fund. In August this year, MicroCyto secured tens of millions of yuan in additional funding, with existing investor Matrix Partners China increasing its investment.

Supported by its team and capital investors, MicroCyto is dedicated to producing various compounds through low-carbon, energy-efficient, and sustainable methods for applications in pharmaceuticals, daily chemicals, agriculture, food, animal feed, and materials. By achieving total biosynthetic pathways for bioactive natural products, it replaces inefficient traditional production methods such as plant cultivation and extraction or animal tissue extraction. Through the design, directed evolution, and expression optimization of key enzymes, it innovates organic synthesis routes for active pharmaceutical ingredients (APIs), reducing production costs while avoiding environmental pollution associated with chemical synthesis processes.

Currently, MicroCyto has successfully established an engineered cell analysis and testing platform as well as a multi-dimensional production process scale-up platform. Its technical platforms are characterized by universality, strong adaptability, broad scalability, modularity, and standardization. MicroCyto has mastered multiple world-leading foundational technologies in synthetic biology. Its R&D center in Changping, Beijing, is capable of designing and developing strains for biomanufacturing, while seamlessly bridging the gap from laboratory-scale technologies to large-scale mass production.

Regarding the refinement and development of technology platforms, Liu Bo emphasized that, from a holistic perspective, the upstream segment of synthetic biology often involves cutting-edge life sciences, such as gene editing and cell engineering, while the downstream segment relies on traditional fermentation engineering."In terms of technological innovation, refinement, and the establishment of barriers to entry, it is evident that there are greater opportunities on the front end."

In addition to its unique technological architecture, MicroCyto also differs from most startups in its strategic layout. During the early stages of entrepreneurship, many companies tend to develop only a limited number of pipelines to balance risk and R&D costs. Once these initial pipelines generate revenue, they then expand their industrial portfolio comprehensively through their technology platforms, investments, or mergers and acquisitions.

However, MicroCyto is different; from the outset, it has extensively laid out its presence in fields such as pharmaceuticals, daily chemicals, agriculture, food, animal feed, and materials. Dr. Liu Bo explained this by saying, “If you come to our company, you will understand.”

On the glass facade of MicroCyto, there is a large metabolic network diagram.This diagram illustrates how a cell can synthesize different compounds through various metabolic pathways for applications in diverse fields, as determined by the inherent properties of the compounds themselves. MicroCyto’s current endeavor is to manufacture these compounds with greater efficiency and at lower cost. Therefore, MicroCyto’s strategic layout is not fragmented or chaotic, but rather coherent and consistent.

Metabolic Network Diagram, Source: MicroCyto

This has also given rise to another critical issue in the field of synthetic biology: product selection.Dr. Liu Bo joked, “Product selection is actually a luxury, because its premise is that you have options to choose from.”

In terms of product selection, MicroCyto adheres to the following four principles:

First, the product must have genuine and existing market demand.rather than the unmet market demands for “anti-cancer” and “healthcare” benefits touted in some medical literature. “Many startups, after targeting emerging fields, attempt to ‘educate’ consumers, but most end up being harshly ‘educated’ by consumers instead.”

Second, the integration of synthetic biology will inevitably bring about significant changes and advancements in the products manufactured by enterprises.If a product can be manufactured using both synthetic biology and chemical engineering technologies, and companies upgrade or iterate their technology merely for storytelling purposes without clear advantages in cost or technical performance, they are highly unlikely to “win” against chemical industry giants.

Third,In recent years, the industry has been rife with the claim that “synthetic biology can create everything,” but in reality,Enterprises must accurately define the boundaries of their capabilities and build their own competitive moats,“No matter the technology or product, given sufficient time, it is likely to be caught up with or surpassed. However, we should identify our core strengths before competitors close the gap, thereby securing the time and space necessary for the company’s survival and growth.”

Fourth,It is also the point most easily overlooked by many enterprises:Enterprises need to consider their own scale and capabilities when planning for future development.“In the later stages of a startup, many issues are not related to scientific research or technology, but rather to human resources, management, strategy, and other areas. We need to continuously adjust our product layout and development plans based on real-world circumstances.”

Under the aforementioned technologies and logic,MicroCyto has established a product portfolio encompassing sugar alcohols and rare sugars such as mannitol and allulose; natural pigments including lutein, zeaxanthin, lycopene, and capsanthin; and functional ingredients for animal nutrition, food, and health supplements.

Among its extensive product pipeline, the mannitol technology has advanced the most rapidly. MicroCyto is the first company globally to achieve mass production using biosynthetic mannitol technology, achieving a conversion rate of 99% and a purity level of 99.9%. Currently, MicroCyto’s mannitol technology has been scaled up for mass production at contract manufacturing facilities, with product quality recognized by multiple international clients, thereby completing the commercial loop encompassing R&D, production, and sales.

On the path to industrialization, MicroCyto’s different products will adopt distinct commercialization strategies:For high-value-added products with small production scales, MicroCyto prioritizes self-built facilities for manufacturing. For bulk products requiring substantial capital expenditure, MicroCyto chooses to collaborate with well-established industry leaders to jointly achieve industrialization.

As early as November this year, MicroCyto entered into a partnership with Sinopharm International.In the Beidaihe New Area, a national-level demonstration zone for the health industry, Sinopharm MicroCyto Technology (Qinhuangdao) Co., Ltd. has been registered and established. The first collaborative project between the two parties, allulose, has completed pilot-scale trials, and regulatory filings have been initiated globally. Small-scale trial production is currently underway, with an annual biological manufacturing capacity of 30,000 metric tons of allulose already secured, which can be rapidly expanded to 60,000 metric tons.

MicroCyto’s inaugural product targets the innate human craving for sweetness, representing a vast market opportunity. Statistics indicate that global annual consumption of sucrose amounts to approximately 180 million tons, alongside 20 million tons of high-fructose corn syrup (HFCS). In China alone, annual HFCS consumption reaches 5 million tons. Excessive sugar intake is a primary driver of obesity and constitutes a significant adverse factor in the management and recovery of diabetes and cardiovascular diseases.

Allulose is a monosaccharide that occurs naturally in trace amounts, representing the class of rare natural sugars. It is found only in small quantities in dried fruits such as dried figs, hence its alternative name, "fig sugar." Allulose has a sweetness profile similar to sucrose but contains virtually no calories.The study also found that allulose promotes normal insulin secretion and reduces intestinal glucose absorption, making it diabetes-friendly while aiding in weight management. Allulose can be widely used in culinary cooking, dairy products, beverages, baking, and other applications, and is regarded as the most promising next-generation “healthy sugar.”

In 2019, after the U.S. FDA announced that the low-calorie sweetener D-allulose would be excluded from “Added Sugars” and “Total Sugars” labeling, new food and beverage products in the United States began to extensively incorporate D-allulose. In North America, the number of new products containing D-allulose in 2020 tripled compared with 2019. According to SPINS data, sales of D-allulose in the North American market grew by 164.2% in the first half of 2022.

Currently, the direct raw material for the industrial production of allulose is fructose, which is produced through epimerase catalysis combined with industrial chromatographic separation. This process suffers from issues such as high raw material costs, low enzymatic conversion efficiency, and high downstream separation costs, resulting in persistently high production costs for allulose and limiting its downstream application scenarios.

MicroCyto, leveraging its synthetic biology R&D platform, has exclusively developed a global first-in-class fermentation-based biomanufacturing technology for allulose. By identifying suitable genes from nature and employing strategies such as AI-driven design, modular gene assembly, enzyme engineering and screening, MicroCyto has integrated a novel allulose biosynthetic pathway into GRAS-certified strains. This innovation enables high-efficiency fermentative production of allulose using glucose or crude sucrose as feedstocks, allowing for direct product crystallization without the need for complex chromatographic separation.

As the production process is similar to that of many traditional fermented products, MicroCyto’s novel biosynthetic technology for allulose can revitalize China’s vast fermentation capacity, significantly reduce the production cost of allulose, and lay the foundation for allulose to become the third widely used bulk sugar after sucrose and high-fructose corn syrup.

In addition to collaborating with renowned enterprises in China’s general health sector, MicroCyto was crowned champion of the “Foreseeing New R&D” track at L'Oréal North Asia’s Big Bang Beauty Tech Creation Camp this November, jointly seeking greener and low-carbon solutions. MicroCyto’s participation in L'Oréal’s ESG initiatives stems from the company’s commitment under its “L'Oréal for the Future” program: “By 2030, 100% of bio-based ingredients in our formulas will be traceable and sourced from sustainable origins; by 2030, 95% of ingredients in our formulas will be bio-based, derived from abundant minerals or circular processes.”

Dr. Liu Bo told VCBeat, “Our synthetic biology technology platform is well-positioned to address some of the pain points L’Oréal faces in sourcing bio-based ingredients. Meanwhile, through collaborations with various international consumer goods giants, MicroCyto has not only validated its own technology platform but also gained valuable insights into product portfolio strategy and development strategies.”

Finally, regarding the company’s future goals and plans, Dr. Liu Bo joked, “The short-term goal is, of course, to ensure the company’s survival and to rapidly establish a closed-loop process from R&D to production to market.”

Beyond the company’s development goals, Dr. Liu Bo remarked, “In addition to drug development, another aspiration of life science professionals is to return material production to nature. This is the goal that MicroCyto is striving to achieve.”