With the increasing demand for food safety, health and sustainability, the main products of various businesses are "plant substitute protein" gradually entering people’s lives: KFC launched "planting golden chicken nuggets", launched "Future Meat Burger" in cooperation with Naixue Tea and Hi Tea on Monday, and Unilever and Burger King jointly launched "Zhenxiang Plant-based Royal Fort".
Nowadays, human beings are facing great practical challenges such as lack of healthy food, greenhouse effect, environmental pollution and energy crisis. Substitute protein is becoming the third choice besides vegetarian and animal meat.
And a microorganism called "microalgae" is becoming one of the effective ways to realize global sustainable development. Microalgae, as its name implies, are tiny algae invisible to the naked eye.
The application of microalgae is very extensive, especially the microalgae-based protein, which is a raw material of food, has a better taste and no allergens, and its essential amino acid content exceeds that of soybean protein and yeast protein.
Figure | Sinian algae fossils (left) and microalgae microscopic cells (right) (source: interviewee)
However, at present, the attention of microalgae industry is relatively low. From the scientific source, it is not as easy to harvest scientific research results as model microorganisms such as large intestine and yeast in the field of synthetic biology.
According to public information, there are more than 300,000 species of microalgae, of which 30,000 species are recorded, but only about 15 species of economic microalgae are currently used in the fields of food, health care products and medicine.
Xiao Yibo, Ph.D. in Biology in Tsinghua University and founder & CEO of Yuanyu Bio, believes that the overall research team in this field is not so "vast", but at the same time, there are no such noisy interference factors in this field, and the judgment of whether the scientific research is good or not will be more obvious. The biggest opportunity for commercialization may lie in the subversion of traditional agriculture.
"So,Microalgae can be one of the ways to realize modern agriculture, and the most reasonable and clearly foreseen opportunity for its final application may appear in the field of substitute proteins. "
Became attached to microalgae, assisted by advanced technology of two microalgae laboratories for nearly 30 years.
Compared with microorganisms, animals and higher plant cells, the molecular transformation technology of microalgae cells started late and developed the slowest. Moreover, the biomass of microalgae in autotrophic metabolism mode is extremely low, which limits the commercial application of microalgae.
The two microalgae laboratories from Tsinghua University can effectively solve the bottleneck problem of microalgae industry, and their contributions in the microalgae field have been recognized worldwide.
"These two microalgae laboratories are Pan Junmin Laboratory and Wu Qingyu Laboratory respectively. They have the most advanced microalgae synthetic biology technology and microalgae engineering scale production technology respectively, and they have been deeply cultivated in the microalgae field for nearly 30 years." Xiao Yibo told DeepTech.
Photo Microalgae Sampling (Source: Respondents)
Professor Pan Junmin is a permanent professor in Tsinghua University, distinguished professor, a Changjiang scholar in the Ministry of Education, a winner of the National Outstanding Youth Fund, and a member of the editorial board of several international journals (including the Nobel Prize winner Xie Keman); Professor Wu Qingyu is a permanent professor in Tsinghua University, the chief scientist of the 973 and 863 projects, the winner of the National Outstanding Youth Fund, the winner of the first national famous teacher award in colleges and universities, and the winner of the national "100 million talents project".
Both professors are authoritative experts in the field of microalgae, and their main research interests are the synthetic biology of Chlamydomonas reinhardtii and the industrial production of Chlorella primitive.
The application of gene knockout and transformation technology in the field of microalgae is very immature, and Professor Pan Junmin’s research group is the first batch of laboratories that can be used as routine technology, which can be described as the "leader" in microalgae research.
Pan Junmin’s laboratory used Chlamydomonas reinhardtii to study the mechanism of flagella assembly and movement, published a series of high-level papers, accumulated very mature microalgae molecular technologies, and integrated these technologies into microalgae synthetic biology.
As early as 2006, Wu Qing Yu Laboratory published the world’s first research paper "biodiesel production from heterogeneous microalgal oil", which was cited for 941 times. One of the core problems in biodiesel production is to realize high-density fermentation of microalgae.
Professor Wu Qing Yu’s research group was the first group to realize the high-density culture of microalgae. They made the biomass of heterotrophic microalgae exceed 100g/L (most autotrophic microalgae biomass is less than 1g/L), and developed a series of facultative heterotrophic and heterotrophic processes, which realized the rapid accumulation of biomass and metabolites and the efficient fixation of CO.
Tu Wei Xiao Yibo (Source: Respondent)
He hit it off with microalgae and has been fighting for the cause of microalgae ever since. The reason for making such a choice is actually inseparable from Xiao Yibo’s family environment, his own preferences and academic experience.
Xiao Yibo was born in a worker’s family, and his mother occasionally took him to work. As a result, Xiao Yibo had more opportunities to come into contact with large-scale automated machinery and equipment since he was a child. Since then, the basic concept of industrial production has been planted in his heart like a seed.
Xiao Yibo, a undergraduate majoring in bioengineering at Northeast Agricultural University, was sent to Tsinghua University for a doctorate with excellent results. Out of strong interest in biological resources, he and Professor Wu Qingyu chose each other and became attached to microalgae from then on.
During his doctoral studies, whenever he encountered difficulties in molecular biology of microalgae, Xiao Yibo would often ask Professor Pan Junmin for advice. Professor Pan Junmin also liked to listen to his ideas about microalgae industry and discuss them together.
In Xiao Yibo’s view, scientific research has many dimensions: universities and research institutes, commercial companies, government departments and so on. In the industrialized business environment, it is more suitable for him to create new things and bring economic value by limiting his own ideas less and promoting the project faster.
Xiao Yibo said that compared with the biomedical industry, the microalgae circle is very small, which gives him a particularly strong sense of mission. "As a closed disciple of the mentor, I don’t have to inherit the research career of microalgae in colleges and universities, and I can also inherit the spirit of Tsinghua in the direction of industrialization and make it bigger and stronger."
Some members of Tu Yuan’s biological team (Source: Respondents)
At the end of 2020, after years of project attempts and work experience, Xiao Yibo’s idea of industrialization gradually matured.Xiao yiboCreate meta-breeding organismsHe took the baton from his mentor and shouldered the mission and responsibility of developing microalgae industry.
Professor Pan Junmin and Professor Wu Qing Yu, two authoritative experts, provided strong technical support for the development of metazoa. One was the chief scientist and the other was the chief consultant, which just corresponded to the upstream microalgae biotechnology and downstream large-scale production technology.
"I am honored to have in-depth cooperation with two professors and invite them to contribute their wisdom to microalgae industrialization and use advanced technology to open a new era of microalgae industry." Xiao Yibo said.
A new track for the global algae product market of 100 billion yuan has gradually taken shape.
With the continuous breakthrough of microalgae biotechnology, microalgae are entering human life step by step, and its more value is gradually highlighted.
In addition to microalgae protein, the content of monounsaturated fatty acid oleic acid in microalgae is higher than other vegetable oils, and the smoke point is higher, which is a high-quality edible oil source. There are other high-value products, such as astaxanthin, β-carotene, lutein, polysaccharide and so on.
In addition, microalgae is a sustainable biological resource for producing polyunsaturated fatty acids DHA and EPA, while DHA and EPA in deep-sea fish oil are obtained by ingesting microalgae, and the algae-derived DHA and EPA are more environmentally friendly and safer to eat.
Xiao Yibo told DeepTech,As a photosynthetic cell factory, microalgae have many natural product metabolic pathways or precursors of higher plants. By means of synthetic biology, it is expected that medicinal compounds such as paclitaxel, crocin and artemisinin can be synthesized, and high-efficiency and low-cost production can be realized.
He said that microalgae have also shown great potential in drug delivery, antimicrobial peptide expression, trauma dressing and other directions, and these innovative applications are also the focus of metazoa.
Photo: Microalgae Culture in Laboratory (Source: Respondents)
Although the prospect is broad, as far as the global microalgae market is concerned, the industrialization of microalgae is developing slowly, and the long-term pain point problem needs to be solved urgently. At the same time, there is a serious lack of high value-added deep-processed products and strong competitive independent brands in the market, so the microalgae industrialization market needs to be developed urgently.
On the other hand, the large-scale production mode of microalgae is backward and the production capacity is low. Most microalgae cultivation methods are still biased towards agricultural production, facing problems such as large area, lack of unified standards and rules, difficult quality assurance, and chaotic market order.
It is understood that there are more than 2,000 enterprises active in microalgae production or processing in the world, while there are less than 100 in China, with an annual output of only 12,000 tons.
Among them, 80% belong to spirulina, and most enterprises adopt open system or semi-closed system, which occupies a large area and cannot guarantee the quality, so it is difficult to realize large-scale industrial production.
(Source: Respondents)
Undoubtedly, powerful microalgae are closely linked with sustainable biological resources, great health, cleanliness, allergen-free, vegan diet, carbon neutrality, plant-based protein substitutes and many other fields, and will certainly attract capital accumulation in the future.
According to reports, in 2018, the global market value of algae products was 33.9 billion US dollars, and it is expected to reach 56.5 billion US dollars by 2027. A brand-new huge track is gradually taking shape.
Whoever enters this new track first will be more likely to get more say in the future market competition.
Create a microalgae CDMO platform, specializing in replacing proteins.
Due to the lack of capital to promote the microalgae market in China, the technology update of enterprises is slow, and the development of microalgae industry is deadlocked, so it is urgent for someone to "stand up" to break the situation.
In Xiao Yibo’s view, it is difficult to improve the quality of microalgae, the scale of production is difficult to expand, the cost cannot be reduced, and the iteration of technology update is slow. Therefore,He believes that "small workshop-style" microalgae enterprises will be difficult to survive in the future, and the platform integrating technology research and development and production technology will become the mainstream.
Therefore, after graduation, Xiao Yibo quickly exerted his own mobility, combined academic knowledge with real industry, and with the assistance of excellent team and advanced technology, he founded metazoa and built a platform for microalgae synthetic organism CDMO (contract development manufacturing organization).
"We have accumulated many years in Tsinghua, mastered many pilot-scale production processes of microalgae and their products, and have many reliable partners in equipment development and factory construction, and the commercial barriers of the CDMO platform are higher. And with the gradual opening of the application scenario, the explosive nature of the CDMO platform will be stronger. " Xiao Yibo said.
Technical discussion of Tu Yuan’s biological team (source: interviewee)
It is reported that,CDMO platform has two trump cards-microalgae biotechnology platform and modular flexible production platform.
The microalgae biotechnology platform focuses on the development of upstream biology, mainly focusing on the breeding of algae species, the transformation of synthetic biology, and the development of laboratory experiments. We also carry out research and development of some innovative products, such as microalgae animal vaccines and microalgae antimicrobial peptides.
Modular flexible production platform focuses on downstream production, for example, photosynthetic heterotrophic integrated reactor independently developed by meta-organisms.
This reactor can not only cultivate autotrophic microalgae, but also carry out heterotrophy or facultative heterotrophy to accelerate the accumulation of microalgae biomass. The advantages of the reactor are very obvious. Independent research and development not only has low cost, but also can be iterated quickly according to the demand.
According to reports, the products and services of Yuanyu Bio point to the direction of food, health care products and skin care products. Xiao Yibo said that their goal is to push microalgae from the production of pure wild algae strains to the rational design of synthetic biology, and at the same time, push the scale production of microalgae from agriculture to industrialization.
The whole process of microalgae culture is fully enclosed on the CDMO platform of metabiotics, and the whole production process is traced back to the source, so that the pollution probability is minimized and the product quality is greatly improved.
This high-standard production mode is expected to re-establish market order and further promote brand-new changes in the industry, so as to be in an advantageous position in future market competition.
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