Production of pharmaceuticals in a specially designed plant factory

Transcription

1 Production of pharmaceuticals in a specially designed plant factory Eiji Goto Environment Control Engineering Graduate School of Horticulture, Japan Presented at the International Congress on Controlled Environment Agriculture, Panama on May, 2015

2 Contents Outline of high value added plant production Pharmaceutical materials production using GM plants Concept of GM plant factory Outline of GM plant factory Production efficiency of photoassimilates per unit light energy among crops Study example: GM rice plant factory Study example: GM strawberry plant factory 2

3 Advancements in the closed-type plant factory - Manipulation of environments The closed system can manipulate both aerial and root zone conditions and create an agrochemical-free environment by blocking pest invasion. The system can provide plants with various artificial stimuli and physiological stresses to maximize the accumulation of the target material. Root zone Aerial Artificial stimuli and physiologic al stresses Hydroponics 3

4 Future perspective of plant factory Present Future Leafy vegetables Nursery plants High value added vegetables Functional phytochemical rich plants Medicinal plants GM plants for pharmaceuticals Plant factory is expected to be a high-functional production system for variety of plant application in the near future. 4

5 Concept of functional high value added plant production using plant factories Creation of functional value added plants Functional food plant(vegetables, fruits, tea, etc.) Manipulation of environment conditions Production of functional value added plants Application of plants Functional food and materials Medicinal plant Semi-closed plant factory Pharmaceuticals, cosmetics, etc. GM crop Function analysis Efficacy evaluation Oral vaccine and functional protein for human and livestock Closed plant factory 5

6 Important points: secondary metabolites or protein (peptide) of the target component Functional value added plants Functional food plant(vegetables, fruits, tea, etc.) Target component Secondary metabolite Application of plants Functional food and materials Medicinal plant Secondary metabolite Pharmaceuticals, cosmetics, etc. GM crop Protein (peptide) Oral vaccine and functional protein for human and livestock 6

7 Contents Outline of high value added plant production Pharmaceutical materials production using GM plants Concept of GM plant factory Outline of GM plant factory Production efficiency of photoassimilates per unit light energy among crops Study example: GM rice plant factory Study example: GM strawberry plant factory 7

8 Pharmaceutical materials production using GM plants in a plant factory GM (genetically modified) plants have recently received much attention because of their use in the production of valuable materials such as pharmaceutical proteins for humans or livestock. Pharmaceutical products that have been or are being developed include oral vaccines for humans or livestock and agents that prevent lifestyle-related diseases. 8

9 Plant-made pharmaceuticals (PMPs) Plant-made pharmaceuticals (PMPs) by using GM plants offer the following advantages over the conventional production methods that use animals or microorganisms (1) low risk of contacting infectious diseases from animals or microorganisms used (2) elimination of the need to maintain a cold chain (3) low production cost (4) ease of large-scale production, etc. 9

10 A closed plant factory is ideal for the production of medicinal substances Advantages of the closed system over open fields include: (1) stable plant production under complete environmental control (2) efficient use of water and CO 2 gas (3) fulfillment of the Good Manufacturing Practice (GMP) specifications (4) low risk of gene diffusion. A closed plant factory is ideal for the production of medicinal substances. 10

11 Advantages of oral vaccine using plants Example: Influenza vaccine A GM rice seed can store the vaccine protein (antigenic protein) in its protein bodies. Number of rice seeds for one administration is approximately 50 seeds. Seed protein Production cost for one administration Conventional (by syringe) 500 yen (= 5 US$) >> Oral vaccine by GM rice yen (= 1 US$) 11

12 Contents Outline of high value added plant production Pharmaceutical materials production using GM plants Concept of GM plant factory Outline of GM plant factory Production efficiency of photoassimilates per unit light energy among crops Study example: GM rice plant factory Study example: GM strawberry plant factory 12

13 Pharmaceutical materials production using GM plants in a plant factory Host plant Concept of GM plant factory GM plant Useful gene(s) Heater, Fan Courcel pump Air generator Vaccine, antibody supplement, etc. Control computer Pump Closed type GM-plant factory Industrialization 13

14 Concept of production of pharmaceutical materials using GM plants Plant cultivation area GM plant Cultivation Harvest Extraction/ purification Biopharmaceutical production area Pharmaceutical materials 14

15 Facility structure and air and water flow in the typical cultivation room of GM plant factory HEPA filter Exhaust air FAN FAN pollen Filter Air conditioner Inedible part Drain water Cultivation room Nutrient solution P Waste Waste tank Air flow Water recycling Water flow Sterilizer 15

16 Pharmaceutical materials developed or being developed in Japan Type Target Material Host plant Oral vaccine human vaccine for cholera rice Pharmaceutical materials Functional protein human influenza vaccine rice livestock vaccine for swine edema disease lettuce livestock bird influenza potato human human thioredoxin lettuce pet animal canine interferon for periodontal disease strawberry human Human adiponectin strawberry human miraclin tomato Goto, E Production of pharmaceutical materials using genetically modified plants grown under artificial lighting. Acta Hort. 907:

17 The world s first plant-derived medicine using a food crop (strawberry) - dog interferon The topical cream for dog gingivitis has been approved in October 2013 by the Japanese government. AIST Japan and Hokusan Co. Ltd. developed the production technology under GMP(Good Manufacturing Practice) regulation in a GM plant factory. GM plant factory (AIST, Japan) National Institute of Advanced Industrial Science and Technology (AIST) Inter-berry 17

18 Contents Outline of high value added plant production Pharmaceutical materials production using GM plants Concept of GM plant factory Outline of GM plant factory Production efficiency of photoassimilates per unit light energy among crops Study example: GM rice plant factory Study example: GM strawberry plant factory 18

19 Question Question: Is there any difference in photosynthesis efficiency per light energy among plants in a closed plant factory? Answer: No. Explanation: next slide Goto, E Acta Hort. 907:

20 Our group have been testing various plants using our closed type plant factories for 10 years Leafy vegetables Fruit vegetables Other vegetables Field crops Medicinal plants Flower plants Others Lettuce, Spinach, Komatsuna, Chinese leaf vegetables, Ocimum basilicum L. (Basil), Eruca vesicaria (Arugula), Corchorus olitorius (Molokheiya), Brassica oleracea var. acephala (Kale) Tomato, Cucumber, Strawberry Radish, Broccoli sprout Rice, Soybean Glycyrrhiza, Red perilla, Japanese mint, Hypericum perforatum (St. John's wort) Phalaenopsis, Eustoma grandiflorum Arabidopsis thaliana 20

21 Comparison of photosynthesis efficiency among food crops based on our experiment data Rice Strawberry Lettuce Tomato Edible biomass gfw m ,200 2,500 7,500 Year-round Cultivation period Days Number of cultivations Edible fresh biomass gfw m -2 /year 2,880 12,800 30,000 30,000 Dry matter ratio % Harvest index Total dry biomass gdw m -2 /year 4,896 2,560 1,667 3,600 Cont. 21

22 Comparison of photosynthesis efficiency among food crops based on our experiment data Rice Strawberry Lettuce Tomato Total dry biomass gdw m -2 /year 4,896 2,560 1,667 3,600 PPF mol m -2 s Light period h /d Daily PPF mol m -2 /d Integrated PPF mol m -2 /year 12,440 6,220 4,150 9,330 Production efficiency of photoassimilates per unit light energy g/mol No difference in efficiency among the crops. 22

23 Production efficiency for air conditioning PPF=200 (Light energy 200) PPF=800 (Light energy 800) COP=4.0 Cooling energy 50 Cooling energy 200 Photoassimilates 100 Lettuce Total energy 250 Photoassimilates 400 Rice Total energy 1,000 No difference in efficiency for lighting and cooling among the crops. 23

24 The viewpoint of productivity and running cost The production efficiency of photoassimilates per unit light energy and the running cost do not differ largely among food crops. Therefore, not only vegetables but also cereals, pulses, potatoes, etc. will be candidate crops in a closed plant factory. 24

25 Pharmaceutical materials developed or being developed in Japan Type Target Material Host plant Oral vaccine human vaccine for cholera rice Pharmaceutical materials Functional protein human influenza vaccine rice livestock vaccine for swine edema disease lettuce livestock bird influenza potato human human thioredoxin lettuce pet animal canine interferon for periodontal disease strawberry human Human adiponectin strawberry human miraclin tomato Goto, E Production of pharmaceutical materials using genetically modified plants grown under artificial lighting. Acta Hort. 907:

26 Contents Outline of high value added plant production Pharmaceutical materials production using GM plants Concept of GM plant factory Outline of GM plant factory Production efficiency of photoassimilates per unit light energy among crops Study example: GM rice plant factory Study example: GM strawberry plant factory 26

27 A trial of production of the rice in a plant factory oral vaccine Target examples 1) vaccine for cholera 2) influenza vaccine Vaccine antigen protein gene gene GM rice Seed preparation GM rice cultivation system with hydroponics Day 49 Day 41 Day 30 Germination Day 63 Day 81(Heading) Day 120(Harvest) Vaccine rice 27

28 PPF (mol m -2 s -1 ) Air temperature ( o C) A trial of production of the rice in a plant factory oral vaccine Optimal control of light intensity and period Sunny day in summer Average for 5 months in the paddy field DLI= 43 mol m o C Time (h) 20 o C Fig. Time change of light intensity in Tokyo, Japan. 28

29 PPF (mol m -2 s -1 ) Air temperature ( o C) A trial of production of the rice in a plant factory oral vaccine Optimal control of light intensity and period Average for 5 months GM rice room DLI = 43 mol m -2 /d Time (h) 27 o C constant in the light period We set light intensity and period at optimal ones and also optimize composition and concentration of nutrient solution. 29

30 A trial of production of the rice in a plant factory oral vaccine Rice yield (g/m2) Productivity 1,200 1, Light utilization efficiency PPF Paddy field Planting density(m -2 ) DLI Avg Temp LUE (g/kmol) Optimal control of light intensity and period maximized light utilization efficiency (LUE) for photosynthesis and enhanced growth. Yield of rice in the GM plant factory is % of that in the paddy field. Goto, E Acta Hort. 907:

31 Contents Outline of high value added plant production Pharmaceutical materials production using GM plants Concept of GM plant factory Outline of GM plant factory Production efficiency of photoassimilates per unit light energy among crops Study example: GM rice plant factory Study example: GM strawberry plant factory 31

32 A trial of production of the plant-derived high-value protein in a plant factory - hadi Co-researchers have achieved to introduce # dog interferon, # lactalbmin, # human adiponectin (hadi) related to the functional proteins into an everbearing strawberry (cv. HS138). GM strawberry gene micropropagation 32

33 A trial of production of the plant-derived high-value protein in a plant factory - hadi GM strawberry cultivation system with multi-layer shelves Vegetative growth Acclimatization micropropagated plantlet Large-scale production using a NFT system Flowering and pollination Fruit production Functional protein strawberry 33

34 A trial of production of the plant-derived high-value protein in a plant factory - hadi Effects of light quality (white [W], blue [B], and red [R]) on fresh weight (A) and days from anthesis to harvest (B) of mature fruit in hadi-expressing everbearing strawberries. hadi strawberry grown under blue/red LEDs Blue and red lights produced more fruit than white light. Blue light promoted flowering. Hikosaka, S Environ. Control in Biol. 51:

35 A trial of production of the plant-derived high-value protein in a plant factory - hadi Small Turning Mature Effects of light quality on hadi concentration in hadi-expressing everbearing strawberry fruit at different fruit maturity stages Exposure to red light resulted in the greatest level of functional protein production. Hikosaka, S Environ. Control in Biol. 51:

36 Electric consumption for fruit yield (kwh g -1 ) Electric consumption for hadi yield (kwh µg -1 ) A trial of production of the plant-derived high-value protein in a plant factory - hadi W B R W B R The red light increased hadi accumulation in fruit body and could reduce 38% of electric cost for lighting and air conditioning compared to that of the white light. Yoshida (2013) 36

37 Contents Outline of high value added plant production Pharmaceutical materials production using GM plants Concept of GM plant factory Outline of GM plant factory Production efficiency of photoassimilates per unit light energy among crops Study example: GM rice plant factory Study example: GM strawberry plant factory Conclusions 37

38 Conclusions #1 - advantages of closed plant factory Environmental control such as light and temperature in a plant factory has the potential to increase targeted functional components in plant leaves, fruit, and roots. 38

39 Conclusions #2 - need for joint research To achieve high value added plant production in plant factories, developments in plant research are required from engineering to plant physiological approaches, such as the creation of optimal LED lighting systems, promotion of photosynthesis, control of gene expression, photomorphogenesis, and synthesis of protein and secondary metabolites. Engineering approach Physiological approach 39