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Synthetic biology is considered to be the next generation of technology that can bring about underlying change
Lan Yuxuan and the microstructure team applied from learning to building and application
Rely on China's scientific research strength to expand the downstream industry
Let China move from a fermentation country to a fermentation power
Synthetic biology, which "creates everything from biology", is one of the most rapidly developing emerging frontier interdisciplinary disciplines in recent years. Thanks to the technical foundation laid by genomics and systems biology, as well as the introduction of engineering design cores and mathematical tools, synthetic biology is considered to be the next generation of technology that can bring about fundamental changes.
At present, synthetic biology is blooming at many points, from new materials, biomedicine to energy and environmental protection, Mars migration, etc., and the research results confined to the laboratory are actively looking for landing scenarios.
The convenience brought by the landing of a technology benefits the end consumer, but the twists and turns and hardships in the process of promotion and landing are like grains of sand on the back of the pedestrian carrying the weight, and only the authorities can experience the taste.
One of them is Lan Yuxuan, 25, co-founder and CMO of Microfabrication Factory. In more than a year, from enterprise preparation, financing, scientific research transformation, project construction, site selection and factory construction to trial production and production, challenges one after another.
The 97-year-old Tsinghua Xueba decided to start a business
Beijing Microstructure Factory Biotechnology Co., Ltd. (hereinafter referred to as Microstructure Factory), founded in February 2021, focuses on the transformation and engineering application of halophilic microorganisms, is an enterprise established by the transformation of scientific and technological achievements of Tsinghua University, and is also a start-up company committed to the manufacture of biomaterials and high-value compounds. Based on "next-generation industrial biotechnology", the company has established a technical platform for synthetic biology transformation of Sanomonas.
The founder and chief scientist of Microstructure Factory is Professor Chen Guoqiang, director of Tsinghua Center for Synthetic and Systems Biology, and a pioneer in the field of synthetic biology in China.
Professor Chen Guoqiang, founder and chief scientist of Microstructure Factory
Soon after its establishment, Microstructure Factory received nearly 50 million yuan in angel round financing led by Sequoia Seeds. In January 2022, the company completed another RMB 250 million Series A financing. Synthetic biology has created a rare excitement in the VC/PE circle this year, and interestingly, the financing is rarely concentrated in the early stages. This is in line with the pulse of the development of the industry, and it is also destined to be a difficult but charming journey.
It can be said that Lan Yuxuan, Professor Chen Guoqiang and the microstructure workshop team are a stormy meeting on the road of application and exploration. In a report on Chen Guoqiang's team, People's Daily described it as "37 years to sit on a cold bench" and "Chen Guoqiang, a professor at Tsinghua University and director of the Center for Synthetic and Systems Biology who has been exploring the research and development of degradable biomaterials for 37 years, is close to seeing the light of day this time."
From returning to China in 1994 to start synthetic biology research, to developing PHA production technology in 2003, the laboratory completed open fermentation to produce PHB and P34HB in 2015, and then to mass production testing; From the mass production of 5-ton fermentation tanks to 15 tons and then to 200 tons, the microstructure workshop is another footprint on Professor Chen's road of production, education and research.
Lan Yuxuan is the youngest of the founding team of Microfabrication Factory. Influenced by his family, Lan Yuxuan became interested in life sciences very early, and naturally applied for the School of Life Sciences of Tsinghua University after the college entrance examination, and finally graduated with the top three grades in his grade.
At that time, in Lan Yuxuan's mind, life science was a cool subject, but after entering the university, he found that many studies were far from real industrialization and could not have a direct impact on reality. At that time, Professor Chen Guoqiang happened to have been working on industrial landing, so he found Professor Chen, and his undergraduate thesis was also related to the professor's research.
After graduating from undergraduate school, Lan Yuxuan went to the University of California, Berkeley for further study. Because he knew what he wanted, at Berkeley, half of his courses were applied bioengineering, and the other half was entrepreneurial management at the Haas School of Business.
In Berkeley, he saw that many academic research and development can be quickly landed, but good domestic research can only stop at the laboratory. He realized that there is no shortage of talents in the domestic life science track, but talents who can connect basic science and industry are very scarce.
So, after graduating with a master's degree, when he received an invitation from Professor Chen Guoqiang to start a business, everything happened naturally. When the microstructure factory landed in 2021, he was not yet 24 years old. Lan Yuxuan is positioned in the team to be responsible for product, marketing and business cooperation.
Reimagining a green future with synthetic biology
"Synthetic biotechnology, which has been in the laboratory stage, is now being industrialized much faster and with more opportunities than expected." Lan Yuxuan said, "The current PHA industry is in the market introduction period, which is a blue ocean. However, for the downstream development ability, the scene landing ability is particularly important. Based on the above understanding, Lan Yuxuan should quickly lead the team to find the landing scene and manufacture the appropriate product with the R&D team according to the needs.
The current commercial track of the microstructure factory is PHA (polyhydroxyalkanoate), which is an ace player to replace petroleum-based plastics, and the typical application case is marine degradable PHA plastics. Every year, 8 million tons of plastic waste flows into the ocean, and about 18,000 plastic waste floats in each square kilometer of sea.
PHA, source: Microstructure Workshop
After the degradable plastic made of this material enters the ocean, it can be quickly metabolized by microorganisms in the natural environment as nutrients to achieve biodegradation, with a time ranging from 1-5 years, which is greatly accelerated compared with the degradation cycle of ordinary plastics for hundreds of years.
Coupled with China's "dual carbon" strategy, PHA has become the focus of attention. However, at this stage, PHA is still in the initial stage of the market, and the process is complex, the cost is too high and the pollution problems are one of the reasons restricting the large-scale promotion and application of PHA.
This is also a difficult problem that needs to be challenged in front of the microfabrication team in front of it. From the perspective of the industrial chain, the upstream of PHA is the strain, and then the strain is modified through gene editing technology, followed by fermentation experiments, and then large-scale mass production to obtain the final powder. Finally, it is processed into pellets according to different application scenarios.
Lan Yuxuan said that in the past, changes to materials could only be modified to a certain extent, but synthetic biology has the ability to change, "If we don't know how much our strain can be changed, we may become an ordinary manufacturing enterprise." ”
A variety of PHA products have been industrialized in the microstructure factory, and PHA trimer P34HBHV has been developed, which has the characteristics of good transparency and non-aging.
In mid-2021, Microstructure completed the world's largest mass production test of a PHA fermenter, with a 200 cubic meter tank almost four stories high. "We have been doing mass production capability verification." Lan Yuxuan said. The microstructure factory's 1,000-tonne-per-year plant in Shunyi, Beijing, is already in trial operation and will soon be operational. Previously, Angel Yeast, the world's second largest yeast company, cooperated with Microstructure Factory to promote the project of PHA production base with an annual output of 10,000 tons in Yichang, Hubei Province.
PHA has hundreds of structures, making it have the characteristics of material variability, nonlinear optical properties, piezoelectric properties, gas barrier properties, thermoplasticity and so on. As a thermal processing material, PHA can be used as an environmentally friendly plastic for packaging; Biodegradability and biocompatibility make them bioimplantable materials for medical and therapeutic applications. Potential therapeutic applications for PHA include medical implants such as heart valve tissue engineering, vascular tissue engineering, bone tissue engineering, cartilage tissue engineering, neural catheter tissue engineering, drug delivery vehicle matrix, incision sutures, prosthetic devices, prosthetic patches, slings, cardiovascular meshes, etc.
The microstructure factory is also expanding new products, such as new dimer, trimer and tetramer PHA products, pharmaceutical intermediates tetrahydropyrimidine, nylon 56 precursor pentanediamine, etc., which can be chemically modified to have fluorescence or unsaturated PHA products with some other functional groups to meet special application scenarios such as medical and cosmetology.
Synthetic chemistry has changed our world and brought serious environmental pollution to mankind. Synthetic chemistry produces only a fraction of the material, but enzymes allow organisms to make more potential materials. Synthetic biology can reimagine a new green future by combining various enzymes to make materials that did not exist before.
Connecting science and industry, building for use
From applying what we have learned to applying what we have learned, the mission of Lan Yuxuan and Microstructure Workshop has ushered in new challenges. Around the "landing scene", the micro-structure workshop has made a flat structure to improve efficiency. "We are very technology-oriented. In fact, the specific project requirements correspond to the end performance, that is, the performance of the pellet. The performance of pellets ultimately needs to be pushed upstream – the strain. Only by understanding the strain can it be easy to do subsequent modification. Therefore, this requires that our product and marketing teams must have a strong scientific and technological background, and also need to accurately transmit the needs of customers to the R&D team in technical language. ”
It is understood that relying on the microstructure "next-generation industrial biotechnology" platform, the strain has been continuously iterated to 20 generations, with the deepening of research and development, the new generation of strains can use many waste carbon sources for production, such as straw hydrolysate, kitchen treatment products, waste glycerin, molasses, acetic acid, etc., to achieve "no competition with people for food".
Today, the microstructure workshop has established contact with more than a dozen of the world's top 500 companies and gradually carried out downstream product research and development, which is also the next difficulty that needs to be broken through after the industrialization run. Because the newer a material is, the more important it is to find downstream application scenarios.
In addition, the PHA industry chain determines the age span of the company's employees, the employees of the production and engineering departments who need experience may be the post-70s, and some links need senior people to lead, but the marketing department needs young people who have both an understanding of the industry, active thinking, and strong execution.
Lan Yuxuan's understanding is that once the industrial chain grows and there are innovative breakthroughs at every point, the management model must change, and it is necessary to stimulate the autonomy of employees, so that they feel that they are motivated and closely bound to the interests of the company. He believes that an open communication is more conducive to the development of the current company. He doesn't rule out arguments and disagreements, "There are people on the team who are better than me, and I'm happy. ”
"The mainland has a huge scientific research force, and in the next 3-5 years, many excellent results will gradually go out of the laboratory." But these researchers are more focused on research and development. Engineering experience is relatively lacking. And downstream, we are already a big producer. If we can rely on China's huge scientific research strength and expand the production capacity at the downstream end, the combination of the two will produce strong potential energy, and we can truly move from a fermentation country to a fermentation power. Lan Yuxuan said excitedly.
He believes that at this stage, efforts should be made to consolidate the single product. If the logic of the enterprise is just a substitute for reducing costs and increasing efficiency, then the demand for talent and teams will be different. Before a brand new material landed, there was a blur between the customer and us. Only after many collisions did the blur become clear. The market-oriented team with technical background should quickly clarify the blurred scene, and the engineering team can design, transform and produce according to the demand, so as to open up a variety of downstream scenarios. At present, what Lan Yuxuan hopes to do most is to achieve stable and positive cash flow and survive for a longer period of time in the challenging economic situation.
In his spare time, Lan Yuxuan is a magic enthusiast and likes to study psychology. The second bachelor's degree in undergraduate studies is psychology.
Science fiction writer Arthur C. Clarke once said, "Any sufficiently advanced technology is equivalent to magic." ”
On the road to entrepreneurship, Lan Yuxuan finally found a balance between the two. Build the world in miniature, build things to use. ■
Forbes China exclusive manuscript, please do not reprint without permission
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