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2-12 Kyoto’s RITE: 500fold increase of catechol production by synthetic biology

The Research Institute for Innovative Technologies for the Earth (RITE) in Kansai Science City near Kyoto claims to have achieved a breakthrough in the microbial production of catechol, financially supported by METI’s project house NEDO within the “smart cell” program. In RITE’s and NEDO’s press releases, details to the process are missing except that a modified strain of Corynebacterium glutamicum is used as production strain and multiple basic technologies were used to improve production gradually. The metabolic sketch in the graph may provide some conceptional ideas to specialists in metabolic engineering.

RITE news release, December 2, 2020

NEDO news release, December 2, 2020

© RITE, Kyoto

7-12 NIKON and Tsukuba University analyze physiological state of microorganisms through autofluorescence signatures

Nikon has developed a confocal laser scanning microscope system which allows to analyze the physiological state of cells at high speed in a quantitative manner. The CRIF method (for Confocal Reflection microscopy-assisted single-cell Innate Fluorescence) acquires cell position and morphology by reflection microscopy and autofluorescence signals, which are reconstructed for each cell into a fingerprint.

The figure below shows the change in signatures for Pseudomons putida and Polymyxa during the log and stationary phase: “Average autofluorescence signatures of P.putida and P.polymyxa at each growth stage (top row), classification of cells in logarithmic growth phase and stationary phase by neural network (bottom row) Red: P.putida, Blue: P.polymyxa”

Nikon news release, December 7, 2020

NEDO news release, December 7, 2020

17-2 Shimadzu developed technology to analyze cell metabolites at high speed and with high accuracy

In collaboration with Kobe University and with support of NEDO, the project house of METI, Shimadzu has developed a “Biotransformer Extraction Total System” that can analyze 186 types of water-soluble cell metabolites at once, and a “Metabolome High-throughput evaluation system” that can find promising smart cell candidate cells in as little as one day. By using these systems to acquire enormous amounts of cell characteristics at high speed with high accuracy and design more appropriate metabolic pathways, it is claimed that smart cell candidate cells can be obtained with 20 times higher selection efficiency.

NEDO news release, February 17, 2021Shimadzu press release, February 17, 2021

© Shimadzu Corporation

17-2 Kobe University installs „smart cell” pilot lab

In this pilot lab, supported by funds from NEDO; smart cells can be developed in less than one-fifth of the conventional time by combining proprietary long-chain DNA synthesis technology, high-throughput recombination technology, and high-speed, high-precision cell metabolite measurement technology. By using these systems to acquire enormous amounts of cell characteristics at high speed with high accuracy and design more appropriate metabolic pathways, smart cell candidate cells can be obtained with 20 times higher selection efficiency than before. You can. Since the development of smart cells, which took a long time, can be overwhelmingly shortened, mass production of highly functional substances becomes possible.

NEDO news release, February 17, 2021

© Kobe University, NEDO

18-2 Hokkaido Mitsui Chemicals produces taxan intermediate by plant-cell culture in 800 l bag reactor

Using undifferentiated plant cells from the Yew tree (Genera taxus), Hokkaido Mitsui Chemicals has developed an 800 L single-use bag reactor for their cultivation. In order to prevent the slowly propagating cells from settling down, a special tube was installed at the bottom leading to circulated water flow without using an agitator. Cultured yew cells proliferation was equivalent to that in flasks and eliminated the need for a control unit for the agitator blades. As a result, the cost of equipment was reduced to about one tenth of that of a stainless steel culture tank. The project was supported by NEDO, the project house of METI. The setup is used to produce 10 deacetylbaccatin III, an intermediate for the synthesis of taxane, an anticancer drug.

Mistsui Chemicals news release, February 18, 2021

NEDO news release, February 18, 2021

10 deacetyl baccatin III
© Hokkaido Mitsui Chemicals

25-2 Asahi Kasei Pharma achieves high-yield production of diagnostic enzyme cholesterol esterase using “smart cell” concepts

The enzyme, used for diagnostic assays of cholesterol in blood, is produced by Burkholderia stabilis from which it is secreted. By combining a novel constitutive promoter and functional modification of the host using genomic and expression control information, the company succeeded in constructing a Burkholderia stabilis smart cell with a cholesterol esterase production capacity more than 30 times higher than that of the wild-type strain. The project was supported by METI’s project house NEDO under the “smart cell programme”.

NEDO news release, February 25, 2021

Asahi Kasei news release, February 25, 2021

Two Japanese groups challenge China’s licorice (glycyrrhizin) monopoly

Licorice root containing glycyrrhizin is the most prescribed crude drug in Chinese medicine, included in about 70% of Chinese herbs. It is also used in Kanpo, Japan’s equivalent of TCM. Glycyrrhizin extracted from licorice is 150 to 300 times sweeter than sugar, used as a sweetener and as a remedy to reinforce liver function. In addition, glycyrrhetinic acid, which is obtained by hydrolyzing the sugar chain of glycyrrhizin, is used in anti-inflammatory drugs, cosmetics, and toiletries.

In 2019, over 1000 t of licorice was imported from China to Japan at rising prices, recently 4,287 yen per kilogram (~35 €).

Recently, two Japanese group are engaged to find alternative sources for this valuable compound.

In 2013, Oji, a papermaker, established a Medical Plant Research Institute and started research analyzing the gene expression of licorice under various cultivation conditions. With a new cultivation technique, glycyrrhizic acid content was increased within a short period of 1.5 years from sowing to harvest, and demonstrated in a Hokkaido farm. Next, mechanization technology required for a ha-scale cultivation of licorice (ha scale) was established on two test farms in ​​Hokkaido. In the fall of 2020, Oji Holdings announced that licorice roots could be harvested in the t scale (dry weight).

A second approach by Toshiya MURANAKA and colleagues of Osaka University and RIKEN is based on synthetic biology, using S. cerevisiae. They cloned the CSyGT gene encoding a glucuronosyltransferase from the licorice plant, and expressed it with six other genes into yeast, enabling it to produce about 0.5 mg/L glycyrrhizin from glucose after 5 days of incubation.

Nikkei Biotech news, January 27, 2021, Nature, November 16, 2020.

Japanese Noster Co. commercializes functional fatty acid which suppresses postprandial glucose levels

The product, 10-hydroxy-cis-12-octadecenoic acid (HYA®), had originally been detected as a metabolite of dietary lipids and fatty acids by intestinal bacteria by the group of Jun OGAWA at Kyoto University. Further research at Nitto Pharmaceutical Co. had shown that this fatty acid inhibits the rise of postprandial blood glucose levels. A process has been developed by Noster Co., a subsidiary of Nitto Co., and supported by NEDO, producing HYA®-50 by reacting naturally occurring vegetable oil with lactic acid bacteria at high density, thus reducing the environmental impact of the production process and positioning HYA®-50 as a “green bioproduct”.

NEDO news release, January 19, 2021

Kawasaki Heavy Industries launches first liquid hydrogen carrier tanker

The Japanese CO2 Free Hydrogen Supply Chain Promotion Organization HySTRA (Members: Iwatani Corporation, Kawasaki Heavy Industries Ltd., Shell Japan Corporation, Power Supply Development Corportion) has launched the first liquefied hydrogen carrier ship. It will transport liquefied hydrogen cooled to minus 253 ° C, leading to a volume of 1/800 of the gas at ambient temperature, safely and in large quantities over long distances. The liquefied hydrogen tank has a vacuum insulated double-shell structure with a holding volume of approximately 1,250 m3 and is scheduled to be completed in autumn 2020. After completion, the ship will transport liquefied hydrogen produced in Australia to Japan. Total length is 116 m, width 19 m, depth 4.5 m at full load, gross tonnage 8,000 t. Propulsion is by Diesel engine electric power generation, and voyage speed  is 13 knots.

NEDO news release, December 11, 2019

© NEDO Japan

Osaka University team finds clue in microbiota for rheumatoid arthritis

Based on extracted DNA samples and shotgun sequencing collected from stool of 82 untreated rheumatoid arthritis patients and 42 healthy subjects, the team of OKADA Toshihiro at Osaka University School of Medicine has found that some species of Prevotella are significantly increased in the microbiome of rheumatoid arthritis patients. It could not be concluded whether the increase of Prevotella is the cause or the result of disease. However, since the stool of patients at an early stage was analyzed, the finding may be used as a risk prediction marker. As there was no significant difference in the metagenomic diversity between patients with rheumatoid arthritis and healthy individuals, dysbiosis did not seem to be related to rheumatoid arthritis.

Nikkei Biotech news release, November 11, 2019

Japanese startups develop “lifestyle guidance AI system” using intestinal environment information

Metagen Co. and MOLCURE Co., two Japanese startups, will established an AI-based system that predicts optimal weight loss using information about an individual’s intestinal environment. The AI ​​system will provide guidance and support for improving lifestyle habits (eating and regular exercise) according to the intestinal environment of the individual.

Metagen (Metabologenomics) is active in microbiome analysis, Molcure onantibody-based libraries for metabolite analysis.

The project is supported by NEDO.

NEDO news release, November 14, 2019

NEDO adopts 7 new themes for regional biomass energy use

In a demonstration project, Tottori Prefecture aims to build a biomass energy utilization energy which does not rely any longer on feed-in tariffs and subsidies. In this project, biomass steam boilers will be installed that use building waste chips as fuel, and waste fungal beds for mushroom cultivation.

In addition, the program includes six Business Evaluation projects:

1. Business feasibility evaluation of an energy supply system in an urban area based on ​​liquefied biomethane derived from livestock manure: Hokkaido Air Water Co.

2. Evaluation of feasibility of local biomass bring-in systems and a smart biomass network: Kitahiroshima-cho, Hiroshima University

3. Evaluation of the feasibility of biomass fuel supply utilizing local production resources such as spent fungus: Chubu Electric Power Co., Sea Energy Co.

4. Feasibility evaluation of increasing yield of methane fermentation utilizing high temperature solubilization treatment and lactic acid fermentation technology, for the spread of on-site small methane fermentation system: Vios Inc., Kyoto University Wakayama

5. Business feasibility of local biomass energy recycling by recycling of glycerin-containing waste liquid: Biofuels Giken Kogyo Co., Yamaguchi University 

6. Evaluation of business feasibility of a dry-type methane fermentation batch system using sugar factory sludge and beef cattle manure as main raw materials: North Soil Development Co.

The overall budget for FY2019 is 1.25 billion yen

NEDO news release, October 29, 2019

NEDO starts biojet fuel feasibility test, focus on supply chain

In addition to establishing integrated production technology for pure bio-jet fuel, supply chain construction including raw material procurement, product supply, commercialization schemes and economic efficiency will be considered in order to promote the realization of such market in Japan. Four themes were adopted, and contractors nominated:

1. Gasification / FT synthesis technology (raw materials are cracked into a gas mainly composed of hydrogen and carbon monoxide, and the desired fuel is produced using a catalyst)

Edison Power Co., JXTG Energy Co., Toyama University

2. Microalgae-based biojet fuel (marine diatom green algae)

Power Development Co.

3. Alcohol to JET (ATJ) technology

Mitsui & Co., JXTG Energy Co., All Nippon Airways Co.

4. HEFA technology (hydroprocessed esters and fatty acids from food waste)

Nippon Steel Engineering Co., Tokyo University of Agriculture and Technology, Daiki Axis Co.

The budget for FY2019 is 2.4 billion yen

NEDO news release, October 30, 2019

© NEDO Japan

NEDO establishes Bioeconomy Promotion Office, adds bioeconomic unit at Technology Strategic Research Center

The overall strategic goal is “to realize the world’s most advanced bio economy society in 2030”. New budget requests for FY2020 include 2 billion yen for “Development of bio-based production technology that accelerates the realization of carbon recycling”, 850 million yen for “Development of technology related to cellulose nanofibers”  and 1.83 billion yen for the “Plastic Effective Utilization Advancement Project”.

NEDO news release, October 30, 2019

Hitachi Zosen builds CO2-to-methane (methanation) test facility

A test facility for synthesizing methane from CO2 and hydrogen was completed on the Koshijihara plant site of Nagaoka Mine in Niigata Prefecture. Tests and continuous operation will be conducted through the end of 2019. In this test facility, methane is produced by synthesizing CO2 produced during natural gas production at the Koshijihara Plant and hydrogen produced by water electrolysis by Kokusai Oil Development Teishi Co. 

NEDO news release, October 16, 2019

© NEDO Japan

“Spider silk” containing „moon parka” limited edition on sale from Goldwin, Japan

In collaboration with the startup company Spiber https://www.spiber.jp, Japan’s sportswear producer Goldwin has offered a web-based lottery for the purchase of 50 pieces of a ski jacket named “moon parka” made from 3 layers, the outermost one of Spiber’s “spider silk” protein. Price with tax is 150,000 ¥ (about 1260 €). The two companies had already released a limited edition of 250 T-shirts made from 17.5% “spider silk” and 82.5% cotton by weight in June this year. The price was 25,000 ¥ (about 200 €). In November 2018, Spiber had announced the construction of a production plant for its “spider silk” proteins in Rayong, Thailand, operational in 2021.

Spiber news release, August 29, 2019

© Spiber Co.

Showa Chemical Industry adds woody biomass module to plant’s LNG heat generator

Under a contract from NEDO, the company has put into operation in its Okayama plant a woody biomass heat generator, using surplus woody biomass such as bark produced in local areas. Liquid natural gas (LNG) and heat from woody biomass will be used, according to fluctuations in fuel prices and procurement conditions, for the company’s drying process of diatomaceous earth products. By operating the biomass facility stably, fossil fuel consumption is expected to be reduced by 20% throughout the Okayama Plant, and carbon dioxide generation is expected to be reduced by 1,000 tons per year

Showa Chemical news release, September 4, 2019

© Showa Chemical Industry Co.

Japan’s government tries to popularize genome editing by a “BioStation” website

The website https://bio-sta.jp/contains information on latest breeding results and explains in much detail the technology behind these results. Projects include deletion of target genes which result in tomatoes with high GABA content, potatoes without solanine, and red sea bream with enhanced muscle meat (myostatin knock-out). The secretariat of BioStation is located at the Japan Agriculture, Forestry and Fisheries and Food Industry Technology Promotion Association (JATAFF), a public corporation affiliated with the Ministry of Agriculture, Forestry and Fisheries. The Japanese government sees genome editing technology as a revolutionary “game changer” that will be a driving force for a future bioeconomy. BioStation is intended to increase public acceptance in order to socially implement genome-edited tomatoes, potatoes, red sea bream, etc. that are about to be put to the markets.

Nikkei Biotech news release, September 9, 2019

COTO LABO consortium strives for better life science data

Eight companies have joined Shimadzu Corporation in an attempt to obtain better reproducible data in the life sciences such as drug-related research. 53 ring tests among these companies had shown that reproducibility of data was indeed low. 8 companies (iPS Portal, Earth Environment Service, NTT DATA, Olympus, Kataoka Manufacturing, Taisei Corporation, Hitachi Industrial Equipment Systems, Shimadzu Corporation) have now initiated this new effort to develop next-generation laboratories where “transparency”, “reproducibility” and “efficiency” of life-science related data will be widely improved.

(COTO = communication tool oriented)

Shimadzu news release, May 30, 2019

NEDO consortium improves microbial bioproduction by AI

In this project, it is planned to build a data infrastructure system for collecting and sharing data which correlate optical and electrochemical sensor data that have not yet been used at bio-production sites (bioproduction management using convolutional data). An AI system will be developed that predicts the optimal culture method hitherto not possible with human experience and intuition, with the aim to establish a method that significantly increases culture efficiency providing a common base for production management in the bioeconomy market.

PI is Chitose Research Institute, contractors are

Ajinomoto Co., Inc. (Food)

Kyowa Hakko Bio Co., Ltd. (food and pharmaceuticals)

Mitsui Chemicals, Inc. (Chemicals)

Kaneka Corporation (Chemicals / Pharmaceuticals)

NRI System Techno Co., Ltd. (System)

Nikon Instech Co., Ltd. (Device)

Nagaoka University of Technology (data acquisition development)

The University of Tokyo (data analysis) 

The Project period is FY2019 up to FY2021

NEDO news release, Sept. 6, 2019

Chitose press release, Sept. 10, 2019

© Chitose Research Institute