Team:CAU China/Integrated HP

Integrated HP

Overview & Flowchart

    The core philosophy of our integrated HP is to ensure that our team and society are interrelated. We are open to the feedback from various groups of society to make our projects more complete, as well as what benefits our projects can bring to each stakeholder. When reviewing the past teams’ HP work, we found that many social groups contacted by the team were relatively one-sided, leading to that the feedback received and the changes to the overall design of the project based on feedback were not comprehensive enough. Therefore, before we launched integrated HP, combined with the characteristics of our project and the composition of the analog industry chain, we created a trilateral communication paradigm. We found representatives in all three groups to conduct interviews and talks, which allowed us to link the whole process of our project with different stakeholders. This paradigm may also help the prospective teams.

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    In addition, intergroup communication requires certain skills due to different backgrounds of different groups. Drawing on the experience of the previous team, we used the example put forward by the team San Diego in 2018, and strived to communicate effectively with different parties and establish a benign influence mutually.

    Our project provided not only the innovative ideas for recycling straw and eliminating environmental pollution, but also a prospect of producing high-value products at low cost, driving the formation of new industrial chains and solving employment problems.

    The timeline below summarizes some of our work in human practice and shows how interaction with different groups can make our projects more complete.

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Interview with locals in Handan's villages, Hebei Province

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    As a team from China Agricultural University, our project focused on the handling of stalk at first. Previously we learned that in China's rural areas, many stalks were burned, which was a waste of resources and caused strong environmental pollution. This problem is particularly common in northern China. Therefore, in order to study the recycling and utilization of crop stalks, and to understand the practical problems that farmers will encounter when handling stalks in farming, our team members visited several rural households randomly in rural areas of Handan, Hebei Province. After several discussions, we found that farmers generally felt stalks

degradation is a knotty problem. In recent years, with the improvement of environmental protection requirements in China, the traditional practice of burying and burning stalks through soil is prohibited. Therefore, some small farms can only put the stalks aside and wait for it to be degraded naturally, which usually takes one to two years. Stalks` self-degradation cycle is long and has a negative impact on crop planting, while traditional incineration method is fast but pollutes the environment. We consulted the farmers about the other destinations of crop stalk, and learned that the locals also use straw as a substitute for coal, as feed for livestock, etc. The pie chart below shows the way the public know about straw treatment. However, these treatments all have the problems such as high cost, low added value of output, and difficulty in marketization.

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    The survey made us realize that the straw treatment is indeed a concern, and we have therefore determined the direction of our project.

Interview with Dr. Fangjian Chen in Tianjin Institute of Industrial Biotechnology CAS

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    From talking with Dr. Fangjian Chen, whose research interests are microalgae biochemical engineering and microalgae molecular biology, we learned that the biggest advantage of Haematococcus pluvialis in producing astaxanthin is high safety and high market acceptance. At present, the mainstream of astaxanthin products in the market are all extracted from Haematococcus pluvialis, and it has been qualified for manufacturing health products, medicines and cosmetics. What's more, the net content of astaxanthin in Haematococcus pluvialis is up to 4% to 5%, and activity can be 100%.

    However, astaxanthin produced by Haematococcus pluvialis also has its inherent disadvantages such as its low density, low yield rate, small cells, difficulties in harvest, high cost, and the short supply. In addition, cells do not produce astaxanthin when in green color and they must be induced to become red to produce astaxanthin, which makes the production process more laborious. Chen's lab is trying to improve the astaxanthin production by modifying algae strains and improving microalgae harvesting methods. He also expressed appreciation for our use of synthetic biology to produce astaxanthin, and believed that this is a novel way of producing astaxanthin, which has great prospects.

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Interview with Dr. Xueli Zhang in Tianjin Institute of Industrial Biotechnology CAS

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    We also interviewed Dr. Xueli Zhang, whose research focuses on using microbial metabolic engineering and synthetic biology techniques to build high-efficiency microbial cell factories and produce bulky chemicals, amino acids and high value-added natural products. His research results have applied for 7 PCT patents and 15 Chinese patents, one EU authorization and four Chinese authorizations.

    Our interview mainly focused on the marketization of astaxanthin. Through interview, we learned that the main reason for high cost of astaxanthin lies in both business and technology.

On the technical level, the astaxanthin production rate in Haematococcus pluvialis is low but the production cost is high. On the commercial level, astaxanthin products produced from E. coli and yeast will have a long period to be approved and a poor market acceptance, and are subject to relevant laws and regulations.

    According to Dr. Zhang, the astaxanthin produced by the engineered E. coli cells has the complete activity. Moreover, the endotoxin of the E. coli can be completely removed, and the safety will be guaranteed. With the continuous development of technology, even the technical issues can be eliminated, it remains difficulties for the commercial promotion because it requires the support of market and related regulations.

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Interview with Dr. Yanqin Li in Tianjin Institute of Industrial Biotechnology CAS

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    Dr. Yanqin Li is focusing on using microbial metabolic engineering and synthetic biology techniques to build high-efficiency microbial cell factories and produce high value-added natural products. As her research group has successfully built a high-efficiency microbial cell factory that produces chemicals such as lycopene and β-carotene, we also consulted her opinions about our project.

    We learned that Dr. Li is currently working on the expression of astaxanthin in E. coli, which coincides with our project. So we asked about the experimental procedures and received expl-

icit experimental guidance. Through this interview, some deficiencies in our experimental design were found and we made improvements and adjustments for our further progress.

Interview with Prof. Liangcai Peng from Huazhong Agricultural University

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    Prof. Liangcai Peng from Huazhong Agricultural University is an expert in the field of biomass energy. His team proposed a model of the groove structure of the plant cell wall, and optimized the cell wall structure and composition for easy processing and utilization. The conversation with Prof. Peng gave us a better understanding of the structure of the plant cell wall and laid the foundation for our initial treatment of straws to obtain cellulose. He also gave us the advice on the employment of beta-glucosidase in our cellulose degradation pathway.

Visting Chenguang Biotechnology Group Co., Ltd. (CCGB)

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    After talking with professors from universities and research institutes, we contacted Chenguang Biotechnology Group Co., Ltd. (CCGB) to learn more about the production and sales of astaxanthin and lycopene products in the industry. We visited the company's showroom, R&D lab and workshop. We also learned about the development of CCGB and its industrial layout around the world.

    After a brief show-around, we had an in-depth conversation with Mr. Xiaodong An, the technical director of Chenguang Company, on the production and sales of lycopene and astaxanthin. Their lycopene production route is different from ours. It is based on tomato dregs for the extraction of lycopene and other active ingredients. The raw material and the extraction process are low in cost, easy to obtain, and the product price is not high. However, the production methods of plant extraction also have their drawbacks, such as the impact of planting climate and some poisoned by-product residues. In addition, the process of extracting astaxanthin from Haematococcus pluvialis is complicated, the yield is low, causing the high cost of the production, resulting in a small market demand and difficulties in developing large-scale production. Our project synthesizes lycopene by E. coli degradation of stalks and converts it to astaxanthin in the further steps, which uses synthetic biology to convert wastes into products. This is not only a new way of utilizing straw wastes, but also a new concept of the lycopene and astaxanthin production. Combining this idea with microbial fermentation processes can produce cheap astaxanthin, giving customers more choices and allowing them to discover new demands.

    Of course, there is a long way from the laboratory to the industrial products. We asked Mr. An about the pipeline from market research to the mass production. We learned that in order to develop a new product, the company needs to do a full research on technology, cooperation, customer needs, and pricing. Only after confirming that the product is promising and capable of achieving reliable profits, it will continue to undergo a cycle of small and pilot tests, repeatedly adjust production processes and technologies, and improve technologies and equipment to be suitable for industrial production. At the same time, the product should be tested in real condition to ensure its safety, and the waste in the production process should be properly disposed. After all the requirements are met, large-scale production and sales can be carried out, and the whole cycle is about five years. This process is also applicable to our astaxanthin products to a certain extent, which is of great significance for the application and practice of our projects.

    Finally, we asked about the job arrangement and manpower requirements of the relevant industries, in the hope that the realization of our project plan will lead to the formation of a new industrial chain and solve more employment problems.

Visiting the Yanjing Brewery

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    After learning about the market for products such as astaxanthin, we visited the Yanjing Brewery and learned about the feasibility of fermenter production. The fermenter is about three-floor high and can store tons of broth. Filling and packing process is basically unmanned: from filling to capping, to the number of bottles that are well-separated, the entire process of encapsulation into boxes is carried out on conveyor belts. The belts are uninterrup-

ed and do not conflict with each other. Following the track, watching these from different directions and positions, we realized how systematic it is. During this visit, we also confirmed the feasibility of fermentation production and built the foundation for our fermented production of astaxanthin and other products.

Survey on the Acceptance of Microbial Products

    We also conducted a survey on the acceptance of microbial products for people of all ages. To study what if our products such as astaxanthin produced by E. coli can be employed in the market, we made this questionnaire. The results of this questionnaire can be used to simulate real conditions. We have received 435 filled questionnaires in total, representing 435 individuals participating in our survey. Among the 435 individuals, the proportion of Holding a bachelor degree/Undergraduate students is the largest (62.16%), followed by people with a diploma of high school/vocational and technical colleges (16.51%). The percentage of graduates with a master's degree or above is 14.22%, and the lowest proportion is of people with secondary school education or below (7.11%).

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    From the results of this survey, the majority of participants have a certain degree of understanding of microorganisms (mold, bacteria, yeast, etc.) in all aspects of life, and they have heard about some of the microbiological products sold in the market. Most participants have basic knowledge of medicines, health care products, food, drink and daily necessities produced by microorganisms and they have been exposed to them in their own lives. Few of them know nothing about or have never used the relevant products. It is reasonable to speculate that the main reason for this phenomenon is that these health care products, daily necessities and other products can meet with the increasing needs of the public as well as satisfy the requirement from legislate departments. These products usually have more promotion opportunities, such as through television, the Internet and other channels, so they are more likely to be known by the public.

    However, even if most participants know that some products they use contain elements related to microbial production, they do not know whether there are any differences in nature between the products produced by engineered microorganisms and the products extracted from natural materials. This requires us to spread relevant knowledge to the public and use the media to guide it correctly.

    PS: Partial data analysis from the questionnaires

    Did you know that there are products containing ingredients produced by microorganisms?

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    What kind of products do you know that can contain ingredients produced by microorganisms?

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    Would you accept the inclusion of genetically modified microbial ingredients in your foods, medicines, health products, cosmetics, etc. (1=unacceptable, 5=no problem)?

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