China Unveils World's First Fully Biosynthesized Squalene with FDA-DMF Certification

As early as the 18th century, Norwegian fishermen knew that shark liver oil could accelerate the healing of skin tissue and alleviate respiratory infections. Therefore, shark liver oil has long been regarded as a folk remedy. In 1916, Japanese scientist Tsujimoto discovered a new pale yellow unsaturated hydrocarbon compound in the liver oils of the deep-sea sharks Ai-zamé and Heratsuno-zamé. After isolation and identification, he named it “squalene,” marking the first time squalene came into public view. Since then,Research on squalene has continued uninterrupted for a century, but its application has long been constrained by production capacity limitations.

Natural squalene is primarily derived from marine animals such as sharks and certain plants. However, due to the impact of human activities on animal and ecological conservation, squalene production is increasingly restricted. Although there are up toOver a dozen types, but due to drawbacks such as excessive steps and complex reactions, it is only suitable for laboratory research and cannot realize its industrial application value.

As one of the high-end chemical raw materials, squalane has been in short supply on the market. Squalene and squalane share similarities, yet squalene far surpasses squalane in functionality, primarily due to the unsaturated bonds contained in the squalene molecule, which enable it toImmunity Enhancement, Antioxidant, Hypoxia Tolerance, Skin Protection(UV resistance, moisturization, free radical quenching, and anti-aging) offer unique advantages that squalane cannot match.

In 2023, research and application of squalene reached a turning point. Baikaisheng Biotechnology, an emerging Chinese enterprise, secured the world’s first FDA Drug Master File (DMF) certification for fully biosynthetic, injection-grade squalene. This proprietary synthetic biology technology, combined with high-density fermentation and advanced extraction processes, has made industrial-scale production and clinical application of squalene a reality. It is reported that the company’s product complies with the standards of the European Pharmacopoeia.(Content ≥ 98%), with high production efficiency and infinitely scalable capacity.

Professor Wei Dongzhi, Founder and Director of the Luhua Institute of Biotechnology at East China University of Science and Technology, remained unusually composed in the face of the blockbuster launch of squalene.

He and his team have been deeply engaged in the fields of biocatalysis and synthetic biology for over 30 years, successfully advancing more than 30 products from laboratory research to industrial application. In recognition of these achievements, he has received one Second Prize for National Technological Invention and five First Prizes for Provincial and Ministerial Science and Technology Awards. Upholding the spirit of “pragmatism, innovation, exploration, and progress,” and adhering to the philosophy that “academic papers are by-products of scientific research,” the team he established has built a unique integrated platform covering the upstream, midstream, and downstream segments of biotechnology. This comprehensive approach has naturally facilitated the scaled production and application of numerous products, such as squalene.

Baikaisheng Biotech Wins Approval for the World’s First Fully Biosynthetic Squalene: A Seemingly Sudden Breakthrough That Is, in Fact, the Culmination of Years of Collaborative Effort.

Over the past two years, the team has"Cell Factory"From establishment, fermentation process optimization, and product separation and purification, to process scale-up and the establishment of quality standards, Baikaisheng Biotechnology has achieved multiple milestone technological breakthroughs. Leveraging synthetic biology technologies, complemented by high-density fermentation and advanced extraction processes, Baikaisheng Biotechnology efficiently and specifically synthesizes squalene from common carbon sources.Achieved the world’s first large-scale mass production of biosynthetic squalene.

Wei Dongzhi told VCBeat’s Orange Bureau, “Without the ‘cell factory,’ the synthesis and mass production of squalene might have been delayed by many more years.”

“Cell Factory” is a database that records the manipulation, reactions, and changes of various chassis cells. This database was built upon years of experience accumulated by Wei Dongzhi’s team in the field of synthetic biology. Leveraging this extensive expertise, the team has developed a world-leading synthetic biology platform based on an intelligent design system for biological metabolic networks and gene editing technologies."Organelle Compartmentalization"Cell Factory. The raw materials used in this technology are inexpensive, renewable biomass with a stable supply, which further reduces the cost of squalene synthesis based on this method.

For synthetic biology companies, achieving the synthesis of the target product is merely the first hurdle. The ability to separate and purify the target product from the fermentation broth, as well as to treat the resulting wastewater, directly impacts production costs and market accessibility.

Pilot-scale to mass production is not a simple linear scale-up.In this process, microorganisms must adapt to the industrial environment, particularly addressing challenges such as the instability of microbial cell growth and metabolism and the loss of target genes during large-scale production. Breakthroughs in process development and scale-up have enabled Baikaisheng (Shanghai) Biotechnology Co., Ltd. to build a competitive moat that is difficult for other companies to replicate. However, as a technology-driven enterprise at the forefront of translating scientific achievements into commercial applications, Baikaisheng’s vision extends beyond this. In addition to achieving breakthroughs in production capacity, the company aims to explore the potential applications of squalene in a broader range of fields.

Currently, the application potential of the biological activity of some squalene products on the market has not been fully realized due to issues with purity and production capacity. However, the product purity of Baikaisheng Biological Squalene>98%, it is currently the squalene product with the highest unit content on the market. This high-quality squalene will first enter the pharmaceutical field as a novel adjuvant. Wei Dongzhi revealed, “Based on current clinical data, squalene-containing adjuvants can enhance neutralizing antibody responses by approximately 100-fold and significantly reduce viral load.”

Baikaisheng Biotechnology’s “cell factory” enables the high-efficiency, high-purity, large-scale production of squalene, poised to replace costly production methods such as shark hunting and plant extraction, and usher in a new era of widespread squalene application in vaccine adjuvants, cosmetics, and health supplements.

In Wei Dongzhi’s future roadmap for the synthetic biology platform, the product portfolio extends far beyond squalene to include a series of terpenoids and other compounds. A prominent example is glufosinate-P (L-glufosinate), a currently high-demand herbicide globally; Professor Wei Dongzhi’s team pioneered the world’s first large-scale biological production process for this active ingredient, achieving an annual capacity of 5,000 metric tons.

“Synthetic biology will undoubtedly see more diversified development in the future.”Therefore, he believes that the development of Baikaisheng Biotechnology should also be “diversified.” Rather than focusing on point-to-point outputs in a specific track, Baikaisheng Biotechnology has chosen to pursue multi-domain coverage led by its technology platforms, including its “cell factory,” intelligent design system for biological metabolic networks, and gene editing platform.

Baikaisheng Biotechnology will expand its reach across the pharmaceutical, food, cosmetics, and agricultural sectors. While providing technical support to more enterprises, it will continue to integrate the upstream, midstream, and downstream segments of “R&D–translation–production,” creating innovative products that are independently developed and manufactured.

It was revealed that Baikaisheng Biotechnology plans to promote within 20233-5 unitsThe product is moving toward the application end.

“Looking at multinational corporations worldwide, their success lies not only in decades or even centuries of accumulation, but sustained research and development and innovation may well be the key to their enduring resilience amidst the tides of change,” said Wei Dongzhi.

In his view, it will take some time for the majority of synthetic biology research in China to transition from academic inquiry to large-scale industrial application. This process requires breakthroughs not only in technology and manufacturing processes but also in bridging academic and technological innovations with product development pipelines to meet market demands. This integration represents the institutional innovation in scientific research that Baikaisheng Biotechnology aims to achieve.

“Original innovation is the soul of scientific research and industrial development”, Over four decades of scientific research experience have led Wei Dongzhi to reflect more deeply on original innovation and the translation of scientific research in China.

He noted that many achievements of Chinese scientific research have not been translated into practical applications. This stems from issues in mindset, institutional frameworks, and research directions. However, whether in scientific research or entrepreneurship, one should not be misled by short-term milestones but must keep the ultimate goal in sight and press forward. Stay true to the original aspiration, and you will achieve your final aim.