In order to improve our projects, we have several interviews with experts in Microbiology, Medicine and Food, to collect information about diabetes, sweeteners, advantage of D-psicose as well as market and possible commercialization of D-psicose. Additionally,we visited the elders and patients in Xi'an Jinqiu Nursing Home, Xi’an Jiaotong University community and hospital, to collect their problems on medical treatment and daily diet, as well as to popularize our projects about healthy sugar substitutes D-psicose. In our WeChat public account, we not only introduce and promote the IGEM competition concept and our project, we also regularly post scientific articles in synthetic biology to gradually walk the public into life sciences.

Our human practice work is integrated into different stages of the project. To learn about the possibility of D-psicose as a drug for the treatment of diabetes，We had a deep interview with Dr Guo, who is a doctor for diabetes treatment. To collect some information about the current sweetener market, and situation of sugar production, we visit companies related to sugar production. To investigate the public's perception about sweeteners and predict the future market of our products, D-psicose，we have collected over one thousand questionaires.

Public participation is very important given that the IGEM competition is a competition that was born to solve practical problems. We actively joined various communities to involve the public into our project. Social media like Wechat public account, Twitter, and public mailbox are constantly used to communicate with the public and other teams. We also conducted questionnaires for online and offline surveys. In addition, social practice of IGEM competition is including offering lectures on synthetic biology, visiting nursing homes, and handing out health manuals.

In order to improve our projects, we have several interviews with experts in Microbiology, Medicine and Food, to collect information about diabetes, sweeteners, advantage of D-psicose as well as market and possible commercialization of D-psicose.

Part 1: Diabetes and possible positive effects of D-psicose on diabetes

Prof.Jiankang Liu, Prof.Jianggang Long

Center for Mitochondria Biology and Medicine in Xi’an Jiaotong University

Prof. Liu and Prof. Long are specialists in mitochondria biology and nutrition regulation on aging and metabolic syndrome. We had an interview with them to obtain their professional opinions on nutrition-disorder related diseases and our D-psicose.

Keypoints

• At present, diabetes is a complex disease, which is difficult to recover just using a single food treatment such as D-psicose-containing food.
• Our project to enhance activity of key enzyme for D-psicose production by directed evolution and biosensor system has great potential for diabetes treatment.

They suggested that we need to know more about the toxicity and safety of D-psicose. Can it be used as a medicine instead of just as a sweetener? What’s the detailed mechanisms of D-psicose on diabetes and obesity, which are nutrition-disorder related diseases? How about the market and cost for this rare sugar?
Let us find the answers in the following human practice!

Dr. Hui Guo

Director of endocrinology department in First Affiliated Hospital of Xi'an Jiaotong University

We had a deep interview with Dr Guo, who is a doctor for diabetes treatment, to learn about the possibility of D-psicose as a drug for the treatment of diabetes.

Keypoints

• D-psicose is suitable for the treatment of obesity and almost all types of diabetes (multi-site functions), which is very advantageous as a potential drug.
• Safety of D-psicose is the major concern, and a series of clinical trials is needed before commercialization.
• Diet control is very important to control blood sugar level and its intakes. A reasonable diet pyramid should be paid attention to for the diabetics.

Prof. Yali Zhang & Dr.Ganqiao Ran

Professor major in food and medicine, Xi’an Jiaotong University
an associate professor in Shaanxi Institute of Bio-Agriculture

Prof. Zhang, who focuses her research on the food and medical mechanism of D-psicose, as well as Dr. Gan-Qiao Ran, who works on medical effects and production of D-psicose, introduced us some reported results about detailed effects of D-psicose.

Keypoints

• In rodents, D-psicose is known to inhibit digestive enzymes, including alpha-glucosidase and alpha-amylase. D-psicose also inhibits the absorption of glucose from the intestine by competing with glucose transporter 2 (GLUT2) on the basolateral membrane of intestinal epithelial cells.
• In rats, D-psicose-induced hepatic glucokinase has been reported to improve hepatic glucose utilization.
• Rats fed D-psicose had significantly lower serum insulin and leptin levels. The D-psicose diet significantly reduced liver enzyme activity involved in adipogenesis, while gene expression of fatty acid oxidative transcriptional regulators was enhanced.

[1] Naohito NISHII1)*, Toru NOMIZO1), Satoshi TAKASHIMA1), Tatsuya MATSUBARA1), Masaaki TOKUDA2) and Hitoshi KITAGAWA1),” Effects of D-allulose on glucose metabolism after the administration of sugar or food in healthy dogs” J. Vet. Med. Sci. 78(11): 1657–1662, 2016
[2] Yasuo Nagata,*,†,§ Akane Kanasaki,† Shizuka Tamaru,† and Kazunari Tanaka†,” D‑Psicose, an Epimer of D‑Fructose, Favorably Alters Lipid Metabolism in Sprague−Dawley Rats”, J. Agric. Food Chem. 2015, 63, 3168−3176
[3] Tomonori Kimura M.S.a, *, Akane Kanasaki M.S.a, Noriko Hayashi M.S.a, Takako Yamada M.S.a, Tetsuo Iida Ph.D.a, Yasuo Nagata Ph.D.b, Kazuhiro Okuma Ph.D.a,” D-Allulose enhances postprandial fat oxidation in healthy humans” ,Nutrition 43–44 (2017) 16–20
[4] Akram Hossaina, Fuminori Yamaguchia, Toru Matsunagab, Yuko Hirataa, Kazuyo Kamitoria, Youyi Donga, Li Suia, Ikuko Tsukamotoc, Masaki Uenod, Masaaki Tokudaa,⇑”Rare sugar D-psicose protects pancreas b-islets and thus improves insulin resistance in OLETF rats”, Biochemical and Biophysical Research Communications 425 (2012) 717–723
[5] Tatsuhiro Matsuo1*, Reika Ishii1, Yoko Shirai2 1 “the effects of 90-day feeding of D-psicose syrup in male Wistar rats”, Vol.1, No.2, 66-71 (2011)
[6] akram hossain1,2 Fuminori Yamaguchi1 Kayoko hirose1 Toru Matsunaga3 li sui1 Yuko hirata1 chisato noguchi1 ayako Katagi1 Kazuyo Kamitori1 Youyi Dong1 ikuko Tsukamoto4 Masaaki Tokuda1 “Rare sugar D-psicose prevents progression and development of diabetes in T2DM model Otsuka long-Evans Tokushima Fatty rats”, Drug Design, Development and Therapy 2015:9 525–535

From literatures and information gathered from doctors and professors in medicine and food fields, we know that D-psicose can be used for a potential drug for the treatment of obesity and diabetes. A series of clinical trials is further needed for safety issues. In addition, the market, price, and the current production situation of D-psicose are still needed to be addressed.

Part 2 Market and current production of D-psicose, as well as commercialization of D-psicose

a distinguished research fellow in Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences

Prof Sun worked in Japan Sugar Research Center which is the pioneer in this field, and she has devoted herself into rare sugar research since then, owning a lot of patents for rare sugars. We conducted an interview with her on the application, market share and production of D-psicose.

Keypoints

• D-psicose is by far a perfect substitute for sucrose, not only in taste, sweetness, calorie, but also in food processing. The most similar sugar to D-psicose is tagatose, but it is more expensive, and its comprehensive characteristics are not as good as D-psicose.
• Japan is a pioneer for study of D-psicose, and the three companies to commercialize D-psicose worldwide are Matsutani Chemical Industry Co.,Ltd.(JP)，CJ Cheiljedang Crop.(KR) and Tate & Lyle P.L.C (UK)
• All three commercialized companies for D-psicose use enzymatic production instead of chemical synthesis, which means high activity of key enzyme in D-psicose biosynthesis is essential.
• D-psicose has been approved by FDA in 2011. FDA-related information shows that D-psicose is sufficiently safe to be used in food. In China it is not approved yet.
• D-psicose has been industrialized out of China since FDA’s approval, and hundreds of foods have been added with D-psicose as a sweetener.
• The global market of sugar is more than $10 million per year, of which more than 80% is sucrose. In China, the demand for sucrose is also large and the yield is insufficient.

Thanks to Prof. Sun, it can be concluded that D-psicose is safe to be used in food and has unparalleled advantages over other sugar substitutes! The large sugar market in the world including in China reveals D-psicose will be in a huge demand as a healthy sucrose substitution especially with low production cost. So we are trying to find out the possibility to commercialization of D-psicose in China.

An expert in the transformation of knowledge into practice

We discussed with Dr Lv to explore the possibility of the industrialization of D-psicose to the market as sweetener.

Keypoints

• Lab-scale production process and techniques are the basis for industrialization.
• More detailed analysis of cost, price, market share of D-psicose needs to be conducted before commercialization.
• To start a business, funding, employees, supplies, regulations, property rights issues, etc need to be taken into account, besides techniques.

From Dr. Lv, we have learned that there is still a long way for industrialization of D-psicose, which requires a lot of efforts and collaborations. Our project about directed evolution system of key enzymes for D-psicose and our proposal concerning advantages and market share of D-psicose will also be beneficial to the further commercialization of D-psicose, contributing to a healthier life style.

Part 3 iGEM advices

Some of the team members participated in the summer exchange program in UC Berkeley. Therefore, we had a chance to meet Prof. Terry Johnson, a bioengineering professor who was a judge of iGEM and we exchanged some thoughts with him on iGEM project.

He firstly introduced the previous projects of UC Berkeley. One of which was bio-manufacturing of blue fuel, inspired by massive demand of blue dyes in jeans. Followed by how to organize a good story for a project, he guided us to the techniques of presentation, such as how to be attractive, engaging, confident, enthusiastic, and logical. We benefited a lot from him!

Our product, D-psicose, as a sweetener, has the advantages of high sweetness and low calorie. To collect some information about the current sweetener market, and situation of sugar production, we visit companies related to sugar production. We learned the market demand of sweeteners and transformation of lab-scale achievements to market, and collected professional insights and suggestions on our IGEM project, to better understand the important value and development prospects of D-psicose.

A company that produces and sales kiwi-containing beverage.

Key points of discussion with Director Tan:

• The potential huge market of D-psicose will rely on people in top cities with healthy diet, or the diabetics, who will prefer to buy healthier D-psicose.
• Chinese people always think of sweetener as a bad additives, which is a potential obstacle for the commercialization of sweetener including D-psicose. More popularizations are needed to make healthy sweeteners acceptable.

The company mainly produces enzymatic sugar-containing food products

Key points of discussion with Director Tan:

• D-psicose is advantageous over other sugar substitutes especially in terms of calorie and taste.
• If we want to commercialize our D-psicose in China, the acceptable price is ~20,000 RMB/ton, which means the price of one bottle of D-psicose-containing beverage is ~10 RMB. The visit allows us to better understand market demand and acceptance of D-psicose, which will better improve our products and project.

This activity allows us to better understand the needs of the market, which will better improve our products.

A company produces oligomannose-containing prebiotic products.

Key suggestions about how to transform scientific research into products to market:

• Ideas goes first before experiment and production.
• Refine lab-scale techniques for large-scale production.
• Think more about the market of your products, your advantages and disadvantages
• Finally, the operation of the entire production, marketing, sales etc.

Benefit the old diabetics

There are 425 million diabetics all over the world with continuous increasing. What can our project do for the people with diabetes? D-psicose is reported to control blood sugar level which is beneficial for diabetics. Therefore, We visited the elders and patients in Xi'an Jinqiu Nursing Home, Xi’an Jiaotong University community and hospital, to collect their problems on medical treatment and daily diet, as well as to popularize our projects about healthy sugar substitutes D-psicose. Our visits and activities will bring warmness to the elders, and also provide some advice that can effectively solve their problems. We also designed and handed out brochures for diabetics after communication with them, to make them have clearer insight into scientific and healthy eating habit. Our projects will benefit and help people who are in need.

Xi’an Jiaotong University community and hospital, Xi'an, Shaanxi Province, China

• Most of the elders in the nursing home have diabetes.
• More than half of them usually eat more vegetables and eat less sugar-containing food，pay attention to the level of their blood sugar.
• With the improvement of living conditions, people's concern about health is increasing.
• Most of people support our project about D-psicose and have a positive attitude towards this healthy sweetener, and willing to buy if it is commercialized.
• We got a deeper understanding of the real needs of the elders.

• Based on the literature, we summarize the clinical manifestations and hazards of diabetes and provide eight healthy eating habits.
• Based on the current lifestyle of elders and diabetics, we proposed correct dietary recommendations.
• Reasonable dietary advice for other geriatric diseases such as hypertension are also included in out brochure.
• Advantage and value of D-psicose are also introduced in this brochure.
• The distribution of the brochure makes people have a better understanding of healthy diet and makes more people benefit from our projects.

Questionnaire about sweeteners

Online questionnaire was used to investigate the public's perception about sweeteners and predict the future market of our products, D-psicose.

The pie chart below is the analysis result about some of the questions in the questionnaire.

1. 1. Here are some sweeteners, which one are you familiar with?

   

2. 2. Will you notice the sweetener marked on the package, when you buy food?

   

3. 3. Do you know any alternatives to white sugar?

   

4. 4. Would you mind adding sweeteners to the food?

   

5. 5. D-psicose is a nature sugar with low energy and good taste. Would you like to add it into your food or drink?

   

We received a total of 1121 questionnaires, and most of our respondents are the young and middle-aged people.

After analysis , we found that everyone buys things subjectively without choosing sweeteners. However, more than half said they would mind the use of sweeteners and want their food to have sugar and low energy.

D-psicose is a natural and healthy sugar, yet little is known about it by public. This sugar with a sweetness of 70%-80% of sucrose, and with low calorie as well as possible positive effect on diabetes. So, when are asked “do you want to buy if D-psicose is added to the food”, about half of them choose "Yes". Therefore, we believe that D-psicose is promising to be used in food and will have huge market in the future.

Based on the survey, we summarized the current beverages on the market and counted the sweeteners used in them.

Table1

Advantages and disadvantages of various sweeteners compared with psicose.

TABle2

By investigating the types of sweeteners in different beverages, we found that most soda drinks use a variety of sweeteners and most of the sweeteners currently used are not as sweet as sucrose. Besides, they can cause dangerous side effects to the human body. In contrast, D-psicose has high sweetness, low calories, and no known side effects, which may be a healthy sweetener. This proves that D-psicose has great advantages in entering the market.

The price of D-psicose on Amazon is $12.88, while in China, D-psicose is currently not sold as a sweetener. However, according to our company visits, market professionals told us that d-psicose under 20,000 yuan/ton can be accepted by the market. If D-psicose is added to the beverage as a sweetener, a price of 10 yuan/bottle is acceptable in the market.

Meetups with other iGEM teams

Location: School of life science in USTC, Hefei;
Teams: XJTU-China, USTC, BNU, Jilin-China

iGEMers of Jilin-China, USTC, BNU and XJTU-China had a nice meeting in USTC. Each team presented their projects and had an extensive discussion about ideas, collaborations details in experiment and modeling, and competition details etc. We learn how to prepare our project and how to present our ideas from the discussion.

Location: Shanghai; Teams: More than 60 Chinese teams

CCiC(the Conference of China iGEMer Community)is a seminar attended by China's iGEM teams. As a communication platform for Chinese synthetic biology enthusiasts, CCiC develops in reform and innovation during 5 years. The 5th CCiC was hosted by ShanghaiTech University. There are more than 60 teams participated in the conference, with several more than 500 people. During the five-day meeting, we met and communicated with other iGEMers, exchanging our knowledge and experience. Meanwhile, some seniors in synthetic biology such as Dr. Haoqian Zhang provided us valuable advice. We experienced a grand feast of thinking.