GIL 2026 | Academician Zhao Guoping from the Chinese Academy of Sciences: Synthetic Biology Enables Biomanufacturing — Moving Towards Deep Integration with Innovation and Industrial Chains

Starting from the historical evolution of life sciences and biotechnology, Academician Zhao outlined the origins of synthetic biology globally and in China. He pointed out that life sciences focus on exploring the internal laws of life, while biotechnology is based on biological systems, transforming organisms and processing biological raw materials to create products needed by humans, ultimately achieving technical implementation and industrial engineering applications.

Early human biotechnology was driven by experience and lacked systematic theory, mainly using traditional brewing and fermentation processes to produce classic fermented products such as wine, vinegar, and sauce. In 1680, humans observed microorganisms for the first time, but the internal relationship between microorganisms and fermentation processes was not yet understood. It was Pasteur’s study of the positive and negative cases of wine fermentation that precisely explained the fermentation mechanism and revealed the principle of microbial contamination, establishing the academic foundation for microbial physiological and biochemical research. Subsequently, with the isolation technology of single microbial colonies, the prototype of cloning technology, researchers could accurately distinguish microbial functions and identify pathogenic bacteria, leading to the successful development of tuberculosis vaccines. With Fleming’s discovery of penicillin, antibiotics were introduced, and in 1929, a new era began with microbial secondary metabolism drugs.

Academician Zhao particularly emphasized that vaccines and antibiotics, two disruptive innovations, increased the average human lifespan by ten years. These are the most significant and profound breakthroughs in biotechnology that have empowered human health in modern times. From ancient empirical techniques to modern biengineering, humanity has traveled from “using nature” to “taming and optimizing” and then to “designing and creating.”

Entering the modern biengineering stage, the discovery of the DNA double helix structure in 1953 allowed humans to fully understand the molecular nature of life. Subsequent breakthroughs in DNA recombination, sequencing, and editing technologies enabled the technical foundation for “readable, writable, and editable” genes. In 1974, the early vision of synthetic biology was formally proposed, envisioning the artificial creation of new life systems through biotechnology, leading to important innovations. During the genomics revolution in the 1990s, systems science was officially integrated into life research. At the beginning of the 21st century, the core concept of synthetic biology was established, defining biological systems as disassemblable, designable, and constructible engineering systems, marking a new stage from “discovery and cognition” to “artificial design” and fully empowering modern biomanufacturing and biomedical industry upgrading.

Looking back at China's development journey, China has a rich foundation in synthetic biology. As early as the 1960s, China achieved two significant achievements: the artificial synthesis of bovine insulin and yeast alanine tRNA, demonstrating the strong chemical and biological research capabilities of China. In the 1980s, structural biology developed rapidly. During the 1990s, China actively participated in the International Human Genome Project, enhancing its core competencies in genomics and bioinformatics. In 2005, students from Chinese universities competed in the International Genetically Engineered Machine Competition.iGEMIt aligns with the global cutting-edge innovation system; in 2007, the Chinese Academy of Sciences took the lead in launching a synthetic biology strategic plan; in 2008, events such as the Xiangshan Conference and the Oriental Forum were held successively in China. That same year, the Key Laboratory of Synthetic Biology at the Chinese Academy of Sciences was approved for establishment, marking an important milestone in the early development of this field in China. After 2010, top research institutions from China, the UK, and the US conducted three rounds of joint seminars, focusing on the evolution of synthetic biology technology, the realization of industrial value, and future development directions. By 2012, the development concept, research framework, and innovation system of synthetic biology in China had taken shape.

Academician Zhao also shared valuable experiences of laboratory transformation. In 2008, his team positioned itself on the new track of “synthetic biology” and successfully obtained approval from the Molecular Microbiology Laboratory of the Chinese Academy of Sciences. Behind the name change and timely transformation was a true reflection of the development of synthetic biology research in China from infancy to initial stage. In the early days of the laboratory, it focused on traditional microbial research. Later, the team actively moved beyond their original research comfort zone and spent ten years reconstructing the research system, building engineering platforms, and tackling core technologies. By 2018, the team had achieved four major core breakthroughs in the creation of artificial cell factories for natural products, simultaneously achieving the scientific knowledge goal of “seeing things to know them” and the industrial application goal of “using things for purposes,” completely completing the strategic transformation and capability upgrade of the laboratory and achieving a rebirth of China’s synthetic biology research forces.

Using artificial cell factories for natural products as a practical example, Academician Zhao vividly explained the implementation path of the synthetic biology engineering system. The rareginseng saponin CKis a highly representative transformation achievement. Ginseng saponin is a key active substance in ginseng, and CK (Compound K) is the rarest due to its single sugar group. It is present in very small amounts in natural ginseng but is a key component produced through intestinal metabolism after human consumption of ginseng. Its scientific and industrial value is significant.

To efficiently synthesize this rare component, the research team built a standardized catalytic element database verified through numerous experiments, covering protein sequences, reaction parameters, pH and temperature conditions, and strain characteristics. They also integrated intelligent search and metabolic pathway assistance design tools. Using the “Design-Build-Test-Learn” iterative engineering research paradigm, the team significantly increased the production of ginseng saponin CK, laying a solid foundation for industrialization. However, Academician Zhao cautioned that the increase in strain yield is only a laboratory achievement and requires a complete process transformation and pilot scale-up system for large-scale commercialization. Therefore, the team established the SHENGHE Building in the Shanghai Chemical Park, a professional natural compound biomanufacturing pilot platform. This platform strictly adheres to national security and environmental protection requirements, enabling a transition from milligram to hundred-kilogram scale and achieving dozens to thousands of times capacity expansion. Even after pilot scale-up, it is only the beginning of the industrialization journey. As the poem says, “The road ahead is tough, but we start anew,” and there is still a long road ahead.

In terms of application value, high-purity natural product raw materials have dual empowering advantages: they can serve as lead compounds to help develop new Western medicines, and they can also support the modernization of traditional Chinese medicine research. The academician offered an innovative view: the human gut microbiota is a “natural factory” for the secondary processing of traditional Chinese medicine in the body. Native ginseng saponins contain little CK, and it is metabolized by the gut microbiota after ingestion, producing this active component. After entering the body, traditional Chinese medicine undergoes another “processing” process, which is an important frontier area in current research on the pharmacological mechanisms of traditional Chinese medicine.

Academician Zhao believes that only by obtaining clearly structured and controllable single active substances can we accurately analyze pharmacological targets and establish quantitative quality standards. A complete standard system can also drive continuous improvement of production processes. High-purity raw materials can empower the development of health products, functional foods, and beauty products. For example, using the rare ginseng saponin Rg3 in aliposome formulationcombination with paclitaxel, compared to traditional albumin-bound paclitaxel, can significantly improve treatment efficacy. On one hand, it can target specific receptors and enhance immune function, and on the other hand, it improves the water solubility of chemotherapy drugs, achieving multiple pharmacological effects and having broad market potential in cell protection and innovative health product development.

Academician Zhao emphasized that scientific regulation is the core guarantee for the stable development of the synthetic biology industry.He pointed out that synthetic biology relies heavily on gene editing and transgenic technologies, which are also key areas of biosecurity concern. Without systematic analysis in natural sciences and social sciences, either regulatory gaps leading to safety risks or unreasonable regulations hindering industry development will become obstacles to the development of synthetic biology.

Therefore, Academician Zhao systematically analyzed the three core aspects of scientific regulation:.

• Purified products with clear structures such as chemical active pharmaceutical ingredients, recombinant proteins, and monoclonal antibodies can directly follow existing mature regulatory systems;

• Non-purified products with complex components such as new food ingredients, traditional Chinese medicine health products, and dual-use biotechnologies require careful risk-benefit assessment, drawing on advanced domestic and international regulatory experiences to optimize and adjust existing regulations;

• Disruptive frontier technologies such as transgenic engineered organisms and cell and gene therapy still lack perfect evaluation tools and management systems, and it is necessary to break through existing frameworks and explore new special regulatory paths.

For the long-term development of the industry, Academician Zhao called for accelerating the development of a scientific and feasible risk assessment methodology to accurately identify instability, uncertainty, and safety risks throughout the technology chain, standardizing the entire product launch approval process, and issuing special regulations, technical guidelines, and industry standards. A hierarchical and classified evaluation model should be established for all stages of research, process, and approval, integrating evaluation conclusions with ethical review, product approval, and market application. Based on the characteristics and management requirements of biocatalysis, a continuously improved standard system should be established. Ultimately, a collaborative governance framework involving industry, academia, and government, with extensive public participation, should be created, coordinating the responsibilities of government authorities, research institutions, and industry enterprises, and establishing a regular coordination and consultation mechanism. A modern regulatory system covering all stages of life cycle development should be built to ensure the high-quality, standardized, and sustainable development of the synthetic biology industry in China.

Finally, Academician Zhao provided a systematic outlook on the long-term development of synthetic biology. He suggested that in the face of the wave of artificial intelligence technology, a rational and cautious attitude should be maintained. The underlying foundation of synthetic biology is always the “Design-Build-Test-Learn” paradigm. With the addition of a high-throughput engineering implementation system and AI efficiency enhancement, the disruptive potential of synthetic biology will be greatly unleashed.

Academician Zhao analyzed that the underlying industrial logic from initial raw materials to final products has not changed significantly over time. Starting with biomass resources, industrial raw materials, and carbon dioxide, standardized technical tools are used to design and build functional elements and chassis cells. Then, there are small-scale tests, pilot scale up, compliance regulatory approval, and market promotion, ultimately achieving industrial implementation and scale expansion. AI will run through the entire chain, generating large amounts of standardized high-quality datasets, enabling the deep integration of “white box” theoretical deduction and “black box” data-driven research paradigms, and opening upAI for Sciencethe link between basic research and industrial application of AI for Industry, creating a closed-loop ecosystem from original innovation to commercialization and continuously producing diverse biomanufacturing products.

Reflecting on the objective laws of technology industrialization, Academician Zhao vividly pointed out thatthe achievements of synthetic biology must overcome three difficult barriers when moving from the laboratory to industrial clusters and social benefits: the “death valley” of achievement transformation, the watershed of engineering scale-up, and the “Darwin sea” of market survival of survival of the fittest.The entire implementation path is full of uncertainties and real challenges. Ultimately, the core issue remains the deep integration of the innovation chain and the industrial chain: on one side, there is supply-side technological innovation driven by policy guidance; on the other side, there is demand-driven development. Both need to be organically coordinated, and the capital and financial systems play a key role in connecting the two.

Academician Zhao emphasized the strategic core of independent innovation: “We cannot always use others’ yesterday to decorate our tomorrow. We have no other choice but to follow the path of independent innovation.”

Focusing on the high-quality development of the synthetic biology and biomanufacturing industries, Academician Zhao gave four concrete implementation suggestions:

• Continuously strengthen and enhance the core position of the biomedical and health industries;

• Promote the integration of multiple disciplines and technologies;

• Activate existing scientific and technological infrastructure and new research platforms, and deepen existing resources to improve overall efficiency;

• Improve the industrial ecosystem construction where the innovation chain and the industrial chain coexist. The academician admitted that building a high-quality industrial ecosystem requires the joint efforts of all sectors of society.

Finally, the academician summarized the industry development trend with poetic language: from the challenging journey of “the road ahead is tough” to the vast landscape of “the mountains are like the sea” today, synthetic biology is at a critical turning point from comprehensive basic research to the large-scale health industry. Only by aligning the national modernized governance system, social and economic operation ecosystem with the convergent innovation core of synthetic biology and the potential of the whole industry, can we truly achieve deep integration of the two chains and ultimately reach the ultimate vision of expanding human health protection and enhancing human living and development capabilities.