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Japan to create its bioeconomy from “bio-digital integration” (バイオとデジタルの融合)

The term will serve as a unifying concept leading to “smart cells” of plants and microorganisms by combining genome analysis, genome editing and metabolic engineering of cells supported by robotics, cloud computing, big data informatics and artificial intelligence.  These technologies will allow to modify living cells and improve genomic selection for a wide range of applications in medicine, energy, materials and agriculture. Target organisms will include agricultural plants, livestock, fish and silkworms, and microorganisms used in the production of fermented food, fuel or speciality  products, including process scaling (もの作りmonozukuri = make things).

Details have been summarized in a 44 page report prepared in June 2019 for the EU – Japan Centre, Brussels https://www.eu-japan.eu

https://www8.cao.go.jp/cstp/tyousakai/juyoukadai/nourin/5kai/siryo3.pdf

Smart drones in a 4G LTE network as airborne police: Japan

NEDO, KDDI, Teradrone and SECOM, utilizing a 4 G LTE standard, conducted security experiments on multiple autonomously flying drones in Kanagawa Prefecture and succeeded in remote patrol security. By remote monitoring of camera images installed in the drones from the...

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Dai Nippon Printing: thin and stretchable skin displays

Based on developments at the University of Tokyo (JST ERATO Someya Project*) the company is developing a thin and stretchable skin display which it plans to market within 3 years**. In this device, 16 × 24 px micro light emitting diodes and stretchable wires are...

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Low-pressure ammonia synthesis makes progress

The group around Hideo HOSONO at Tokyo Institute of Technology has succeeded to further optimize a catalyst which permits to produce ammonia from molecular nitrogen and hydrogen at relatively mild conditions (400 C, 0.1 MPa = 1 bar). The best catalyst found so far is...

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18-6 NEDO aviation fuel produced from wood waste and microalgae supplied to scheduled flights

NEDO has commissioned Mitsubishi Power, JERA Corporation, Toyo Engineering, and the Japan Aerospace Exploration Agency (JAXA) for the development of fuel production technology using wood waste as raw material, and IHI Corporation for fuel production technology using microalgae as raw material, within a “Biojet Fuel Production Technology Development Project. The fuel is produced either by gasification of solid woody cellulose, or by hydrogenation refining technology of oil derived from microalgae, both of which have been confirmed to conform to ASTM D7566, the international standard for aviation fuel. Based on the results of the NEDO project, fuel completed with both technologies was supplied to regular flights departing from Tokyo International Airport (Haneda Airport).

[1] Fuel produced from wood waste

Date: June 17, 2021

Flight number: Japan Airlines Flight 515

Segment: Tokyo International Airport to New Chitose Airport

Aircraft: Airbus A350-900

Fuel used Approx. 8,700l

2] Fuel produced from microalgae

(1) Date: June 17, 2021

Flight number: Japan Airlines Flight 515

Segment: Tokyo International Airport to New Chitose Airport

Aircraft: Airbus A350-900

(2) Date: June 17, 2021

Flight name: All Nippon Airways Flight 031

Segment: Tokyo International Airport to Osaka International Airport (Itami Airport)

Aircraft: Boeing 787-8

NEDO news release, June 18, 2021

24-6 Tsukuba University Hospital launches “Genome Dock” service for genome analysis data of healthy people

The service comprises initially 76 genes related to 18 diseases such as tumors, cardiomyopathy, congenital hearing loss, and immune disorders. Among these genes are APC, BRCA1 / 2, RET, SMAD4, TP53 and other genes familiar in cancer medicine, as well as the KCNH2 gene for hereditary arrhythmia / congenital long QT syndrome and the TTR gene for familial amyloidosis. , CYP2C9 gene related to drug metabolism, etc.. Once the test is on track, it is planned to expand to 193 genes and chromosomal structural abnormalities.

Phase 1 is a practical study (feasibility study). Phase 2 starting in July will comprise about 100 people at a cost of 400,000 yen per person. Phase 3, which is scheduled to start in January 2022, will upgrade to the hospital business, and plans for about 1000 people. At this stage, the cost per subject is assumed to be 500,000 to 650,000 yen.

Nikkei Biotech news release, June 24, 2021

11-6 Team at Tokyo University of Agriculture and Technology develops DNA aptamer that enhances luminol reaction more than 300 times

The group around Kazunori IKEBUKURO has used the SELEX method to develop an aptamer which binds to myoglobin and changes the three-dimensional structure of the active site. As a result, the enzymatic activity of myoglobin and the substrate specificity for luminol are increased, so that the luminescence signal generated by the peroxidase reaction over 300 times higher than usual. The group plans to combine their system with an aptamer for a target virus or pathogen so that the three-dimensional structure is assembled in the presence of the target. This would allow virus or pathogen detection technology by light.

Nikkei Biotech, June 11, 2021

10-6 Japan’s NEDO publishes database on current „smart cell projects“ (genome editing etc.)

The database is available from the National Institute of Technology and Evaluation of Products (NITE) under its Data and Biological Resource Platform (DBRP) website https://www.nite.go.jp/nbrc/dbrp/taglist and currently (June 2021) contains the following projects:

Title Proteome analysis_Aspergillus oryzae : Proteome analysis of Aspergillus oryzae

[English] The proteome of Aspergillus oryzae RIB40 (= NBRC 100959) grown under liquid culture and membrane-transfer culture have been analyzed.

Project URL: https://www.nite.go.jp/nbrc/genome/project/proteome/rib40_p.html 

Title Proteome analysis_Brevibacillus brevis : Proteome analysis of Brevibacillus brevis

[English] The proteome of Brevibacillus brevis 47 (= NBRC 100599) grown under T2 medium and minimal medium have been analyzed.

Project URL: https://www.nite.go.jp/nbrc/genome/project/proteome/BB_p.html 

Title Proteome analysis_Aeropyrum pernix : Proteome analysis of Aeropyrum pernix

[English] The proteome of the aerobic hyper-thermophilic crenarchaeon, Aeropyrum pernix K1 (= NBRC 100138) grown at 90 ˚C has been analyzed.

Project URL: https://www.nite.go.jp/nbrc/genome/project/proteome/K1_p.html 

Title Proteome analysis of Methanococcus maripaludis : Proteome analysis of Methanococcus maripaludis

[English] The proteome of methanogenic archaea, Methanococcus maripaludis strain OS7 (= NBRC 103642) with the iron corrosive property and its corrosion-defective mutant OS7mut1 (= NBRC 105638) have been analyzed.

Project URL: https://www.nite.go.jp/nbrc/genome/project/proteome/mm2_p.html 

Title Proteome analysis of Escherichia coli : Proteome analysis of Escherichia coli

[English] The proteome of Escherichia coli K-12 W3110 grown under glucose minimal medium has been analyzed.

Project URL: https://www.nite.go.jp/nbrc/genome/project/proteome/index.html 

Title Proteome analysis of Rhodococcus opacus: Proteome analysis of Rhodococcus opacus

English] The proteome of Rhodococcus opacus B4 (= NBRC 108011) and its mutants have been analyzed.

Project URL: https://www.nite.go.jp/nbrc/genome/project/proteome/B4_p.html 

Title Proteome analysis of Kocuria rhizophila : Proteome analysis of Kocuria rhizophila

[English] The proteome of Kocuria rhizophila DC2201 (= NBRC 103217), which is the bacteria tolerant to organic solvents, grown under several conditions The proteome of Kocuria rhizophila DC2201 (= NBRC 103217), which is the bacterial tolerant to organic solvents, grown under several conditions

Project URL: https://www.nite.go.jp/nbrc/genome/project/proteome/KR_p.html 

Title Proteome analysis of Anaerolinea thermophila: Proteome analysis of Anaerolinea thermophila

[English] The proteome of Anaerolinea thermophila UNI-1 has been analyzed.

Project URL: https://www.nite.go.jp/nbrc/genome/project/proteome/at1_p.html 

Data Title Project (Proteome Analysis_Arthrospira platensis (Spirulina platensis))

[English] The proteome of Arthrospira platensis (Spirulina platensis) NIES-39 have been analyzed.

Project URL: https://www.nite.go.jp/nbrc/genome/project/proteome/apl_p.html 

Title Proteome analysis_Gemmatimonas aurantiaca: Proteome analysis of Gemmatimonas aurantiaca

English] The proteome of Gemmatimonas aurantiaca T-27 have been analyzed.

Project URL: https://www.nite.go.jp/nbrc/genome/project/proteome/ga1_p.html 

Title Proteome analysis of Sulfurisphaera tokodaii: Proteome analysis of Sulfurisphaera tokodaii

English] The proteome of Sulfurisphaera tokodaii strain 7 (Sulfolobus tokodaii strain 7) has been analyzed.

Project URL: https://www.nite.go.jp/nbrc/genome/project/proteome/st7_p.html 

Title Proteome analysis of Caldilinea aerophila: Proteome analysis of Caldilinea aerophila

English] The proteome of Caldilinea aerophila STL-6-O1 (NBRC 104270T) has been analyzed.

Project URL: https://www.nite.go.jp/nbrc/genome/project/proteome/ca1_p.html 

Title Proteome analysis of Tetragenococcus halophilus : Proteome analysis of Tetragenococcus halophilus

[English] We have analyzed the proteome of Tetragenococcus halophilus (= NBRC 12172) cultured with added salt concentration of 0% and 10%.

Project URL: https://www.nite.go.jp/nbrc/genome/project/proteome/th1_p.html 

Institution Name Strain Management Group, Planning and Management Department, Production Control Center, AminoScience Division, Ajinomoto Co.

Title Aquatic Imperfect Bacteria Screening Project

Abstract To create new medical and agricultural resources from aquatic imperfect bacteria known to have unique metabolites, a library of aquatic imperfect bacteria isolated as a screening source

Institution National Institute of Advanced Industrial Science and Technology (AIST)

Title Development of genome and transcriptome analysis technology suitable for information analysis

Abstract In order to realize reliable RNA-Seq analysis, the project aimed to expand the number of RNA reference materials for spike-ins and to apply them to industrial microorganisms, as well as to establish a method for obtaining gene expression information for RNA that is considered to be of low quality by general-purpose evaluation indices.

Project URL: https://www.jba.or.jp/nedo_smartcell/technology/14.php 

Institution Ajinomoto Co.

Title Development of a rapid search technology for DNA sequence factor combinations using the Combi-OGAB method and machine learning

Abstract By creating a microbial library using the Combi-OGAB method and analyzing the data using machine learning, we extracted the laws necessary for gene sequence design and high production of target substances. Specifically, by regulating the expression intensity of limonene biosynthetic enzymes in E. coli, we extracted the bottleneck enzymes and the rules for high production.

Institution Osaka University

Title Proteome analysis technology development

Abstract We constructed a multiple reaction monitoring (MRM) assay to measure the expression levels of E. coli central metabolic enzyme proteins. Specifically, we obtained proteome data by performing nano-LC-MS/MS analysis of tryptic digested samples of E. coli ASKA strain (one gene overexpression strain) and wild strain.

Project URL: https://www.jba.or.jp/nedo_smartcell/technology/16.php 

Institution Name Kobe University

Title Development of high-throughput microbial construction and evaluation technology

Abstract We developed a semi-automated transformation technology that can obtain several thousand transformants at once. Carotenoid pigment (lycopene or β-carotene) biosynthesis pathway plasmids were comprehensively introduced into gene-disrupted strains (approximately 4,000 strains of E. coli and 5,000 strains of budding yeast), and carotenoid productivity was comprehensively evaluated and data obtained by image analysis of bacterial coloration.

Project URL: https://www.jba.or.jp/nedo_smartcell/technology/07.php 

Institution Name Kobe University

Title Metabolome analysis technology development

Abstract Project Summary: In the course of developing analysis technology to obtain metabolome data that contributes to metabolic pathway design with high accuracy and high throughput, we established a metabolome measurement method using LC/MS/MS and developed an “automatic pretreatment system.

Project URL: https://www.jba.or.jp/nedo_smartcell/technology/15.php 

Institution Name University of Tsukuba, Nikon Instec Co.

Title Development of production technologies for high-functional products using plants and other organisms / Development of information analysis systems that contribute to the creation of highly productive microorganisms

Abstract We succeeded in predicting the amount of oil and fat produced by each cell by obtaining the single-cell autofluorescence profile of oil-producing yeast using the single-cell autofluorescence profile analysis platform.

Project URL: https://www.jba.or.jp/nedo_smartcell/technology/17.php 

Organization National Institute of Technology and Evaluation (NITE)

Title Development of design and optimization methods for novel metabolic pathways

Abstract Aiming to design new metabolic pathways for carotenoids and alkaloids using the metabolic pathway design platform tool we developed, we evaluated the carotenoid production culture of NBRC strains, obtained enzyme gene information that is expected to improve the productivity of these substances from genome information, literature and patent information, and verified the introduction effect. In addition, we obtained information on enzyme genes that are expected to improve the production of these substances from genome information, literature, and patent information, and verified the effects of their introduction.

Institution Asahi Kasei Pharma Co.

Title Efficacy verification by improving the productivity of cholesterol esterase

Abstract Cholesterol esterase is used for the diagnosis of blood cholesterol. In order to improve the productivity of cholesterol esterase producing strain Burkholderia stabilis, we conducted genome analysis of the producing bacteria. In addition, DNAseq and RNAseq analyses were conducted to search for genes that contribute to productivity.

Institution Nagaoka University of Technology

Title Validation of simultaneous control of production of useful proteins using filamentous fungi

Abstract T. reesei produces several extracellular enzymes, and omics analysis of the standard strain and the industrial production base strain was conducted in order to vary the production of each enzyme. Gene expression network analysis using the omics data was used to find the factors that change the enzyme components and to verify the disruptive effects.

Project URL: https://www.jba.or.jp/nedo_smartcell/proof/01.php 

Institution Kobe Natural Products Chemistry Ltd. and National Institute of Advanced Industrial Science and Technology

Title Verification of the effectiveness of enzyme design technology using monoterpenoid oxidase such as limonene ~Development of enzyme modification technology using MD simulation~.

Abstract Regioselectivity and productivity are sometimes issues when using enzymatic reactions. Therefore, in collaboration with the National Institute of Advanced Industrial Science and Technology (AIST), we have developed a method for predicting enzyme modification sites that improve reaction regioselectivity using molecular dynamics (MD) simulation. In addition, the oxidation of monoterpenoids such as limonene was used as a model case, and the function of the modified enzyme was evaluated using P450 in the Kobe Natural Products Chemistry cytochrome P450 library.

Project URL: https://www.kncweb.co.jp/technology/bioconversion.html 

Institution Name Mitsubishi Chemical Corporation

Title Validation of Metabolic Analysis Technology by Improving the Productivity of Useful Isoprenoids

Abstract In order to breed microbial strains that produce high levels of isoprenoid compounds, we analyzed the products of various breeding strains and their expression levels under a number of culture conditions, and used the results to extract candidate genes and reactions that contribute to solving bottlenecks.

Institution Name Research Institute of Innovative Technology for the Earth

Title Validation of Metabolic Analysis Technology by Improving the Productivity of Useful Aromatic Compounds Using Bacillus subtilis

Abstract A smart cell design system was verified through the improvement of catechol productivity. In the process, we conducted an omics analysis of catechol-producing strains and shikimic acid-producing strains under various conditions, contributing to the improvement of the accuracy of metabolic pathway design technology, expression control network construction technology, and transporter search technology.

Project URL: https://www.jba.or.jp/nedo_smartcell/proof/02.php 

Institution National Institute of Advanced Industrial Science and Technology

Title Efficacy Verification by Controlling Pigment Production Using Red Yeast Rice Mold

Abstract To improve the productivity of red yeast rice pigment, a natural food pigment produced by red yeast rice mold, we conducted comprehensive gene expression analysis of the reference strain, mutant strains, and validation strains under various culture conditions to verify the effectiveness of genetic modification using a new mathematical model based on expression control network model. In addition, we clarified the pigment synthesis gene cluster and citrinin synthesis gene cluster by draft genome analysis of the reference strain, and constructed a biosynthetic model.

Institution National Institute of Advanced Industrial Science and Technology

Title Validation of a new production method for paprika-derived carotenoids using microorganisms

Abstract Targeting two industrially useful carotenoids (β-cryptoxanthin and lutein) derived from paprika, we selected enzymes involved in the efficient biosynthesis of these carotenoids and verified their production in E. coli and yeast. As a result, we succeeded in producing these two carotenoids in E. coli and yeast.

Project URL: https://www.jba.or.jp/nedo_smartcell/proof/07.php 

Institution Niigata University of Pharmacy and Applied Life Sciences, Nagaoka University of Technology

Title Verification of the efficacy of oils and fats containing ω-3 polyunsaturated fatty acids by improving their productivity

Abstract We attempted to construct eicosapentaenoic acid C20:5 (EPA)-producing strains using two kinds of oil and fat yeasts (Lipomyces starkeyi and Rhodosporidium toruloides) and created EPA-producing L. starkeyi. In addition, we identified genes that improve oil and fat production by constructing an expression regulatory network model using transcriptome analysis data of oil and fat accumulation mutants, metabolome analysis, proteome analysis, and genome comparison analysis, and created a high-producing strain by utilizing these genes. 

Abstracts of related presentations at the Japan Society for Bioscience and Biotechnology 

Development of high oil and fat producing strains of the oil and fat yeast Lipomyces starkeyi (https://ci.nii.ac.jp/search?q=9000291273015) 

Expression analysis of genes related to fat and oil synthesis and degradation in a low-fat accumulation mutant strain of Lipomyces starkeyi (https://ci.nii.ac.jp/search?q=9000316621316) 

Acquisition of fat and oil hyperaccumulating mutant strains of Lipomyces starkeyi using density gradient centrifugation (https://ci.nii.ac.jp/search?q=9000316621322) 

Acquisition of fat and oil hyperaccumulating mutant strains of the industrial oil and fat yeast Lipomyces starkeyi (https://ci.nii.ac.jp/search?q=9000321425083) 

Expression analysis of genes involved in fat and oil accumulation in the oil and fat yeast Rhodosporidium toruloides (https://ci.nii.ac.jp/search?q=9000316621333) 

Improvement of oleaginous yeasts using informatics for the production of functional fats and oils (https://jsbba.bioweb.ne.jp/cgi-bin/jsbba_db/jsbba_summary.cgi?id=58970) 

Identification of genes responsible for low fat accumulation in the oleaginous yeast Lipomyces starkeyi by comparative genomic analysis (https://jsbba.bioweb.ne.jp/cgi-bin/jsbba_db/jsbba_summary.cgi?id=57534) 

Identification and functional analysis of novel regulators of lipid accumulation in the oleaginous yeast Lipomyces starkeyi by comparative genomic analysis (https://jsbba.bioweb.ne.jp/cgi-bin/jsbba_db/jsbba_summary.cgi?id=57532) 

Identification and analysis of the causative gene of lipid hypoaccumulation mutants in the oleaginous yeast Lipomyces starkeyi (https://jsbba.bioweb.ne.jp/cgi-bin/jsbba_db/jsbba_summary.cgi?id=56884)

Project URL: https://www.jba.or.jp/nedo_smartcell/proof/03.php 

Institution Name Ishikawa Prefectural University, Kobe University

Title Validation of a new production method for alkaloids and other compounds using microorganisms

Abstract Five new biosynthetic pathways from tyrosine to 3,4-DHPAA were established by information analysis. In addition, we searched for enzymes with similar functions to tyrosine hydroxylase and monoamine oxidase, which are the rate-limiting reactions in the reticulin biosynthetic pathway, and introduced plasmids. In addition, we constructed a genome-inserted reticulin-producing E. coli strain for practical use, and also produced a genome-inserted tyrosine and dopamine high-producing E. coli strain.

Project URL: https://www.jba.or.jp/nedo_smartcell/proof/04.php 

28-5 Japan starts genomic cohort study involving over 360,000 people

Under an initiative of Japan’s Agency for Medical Research and Development AMED, this collaboration among six institutions and five sites will sequence and mutually utilize genomic cohort data of 366,000 people. The project is expected to promote the elucidation of genetic predisposition affecting the onset of diseases in the Japanese population and the construction of risk prediction models. It will also contribute to next-generation medical care, such as personalized medicine, personalized prevention, and risk prediction tailored to each individual’s constitution. 

Outside of Japan, genomic cohort studies involving several hundred thousand to one million people are The Million Veteran Program (MVP), which started in 2021 in the U.S. with more than 820,000 participants, and the UK Biobank, which started in 2006 in the U.K. and targets British more than 500,000 volunteers.

The DNA microarrays used at the six institutions and five sites are the Geponica array developed by ToMMo for the TMM project and the TMC Illuminas array.

Nikkei Biotech news release, May 28, 2021

3-6 NEDO starts million project on innovative storage batteries (2021 – 2025)

In this project, the partners will conduct R&D of fluoride and zinc anode batteries that can achieve both high energy density and safety while using inexpensive materials with fewer resource constraints than lithium-based batteries. NEDO will work with industry, academia, and government to research and develop common basic technologies that cover everything from materials development to battery design, prototyping, characterization, and analysis, with the aim of maintaining and improving the competitiveness of the automobile and storage battery industries by quickly commercializing these batteries for use in electric and plug-in vehicles. The project will be supported by 11 – 12 billion JP¥ (90 million €)(2021-2025).

Contractors are: Kyoto University (representative institution), Tokyo Institute of Technology, Waseda University, Daikin Industries, Toyota Motor Corporation, Nissan Motor Corporation, Panasonic Corporation, Honda R&D Co. Asahi Kasei, Showa Denko Materials, Nippon Electric, National University Corporation Osaka University, Public University Corporation Osaka, National University Corporation Kanazawa University, National University Corporation Kyushu University, National University Corporation The University of Tokyo, National University Corporation Tohoku University, National University Corporation Tokai National University Organization, National University Corporation Nagoya Institute of Technology, Hyogo Public University Corporation, National University Corporation Mie University, National University Corporation Yamaguchi University, Ritsumeikan Corporation The University of Tokyo, Tokai National University, Nagoya Institute of Technology, Hyogo Prefectural Public Corporation, Mie University, Yamaguchi University, Ritsumeikan University, National Institute of Advanced Industrial Science and Technology, High Energy Accelerator Research Organization, and Fine Ceramics Center.

NEDO news release, June 3, 2021

© NEDO Japan

18-5 Researchers at CiRA develop transform universal iPS cells for allogenic T-cell-based cancer immunotherapy

A research group led by Professor Shin KANEKO at the Center for iPS Cell Research and Application (CiRA), Kyoto University, have developed a universal iPS cell in which multiple genes were modified by genome editing, e. g., by knocking out the PVR gene related to the regulation of NK cells, so that it can be transplanted to a wide range of recipients regardless of the genotype of the donor’s human leukocyte antigen (HLA). Next, the research team induced differentiation of this cell type into T cells. A CAR gene targeting CD20 was introduced with a viral vector, and CAR-T therapy was evaluated in a mouse model.

Nikkei Biotech news release, May 18, 2021

30-4 Sanatec starts to distribute free seedlings of genome-edited “Sicilian Rouge High GABA” tomatos

Sanatec Seeds, a venture spin-out of the Japan’s University of Tsukuba, is the first company in the world to commercialize genome-edited tomatoes, “Sicilian Rouge High GABA”

“Sicilian Rouge High GABA” is a strain (variety registration pending) that contains four to five times more gamma aminobutyric acid (GABA), an antihypertensive, than its parent strain, Sicilian Rouge CF. This is the first generation (F1) hybrid created by crossing Sicilian Rouge CF with the genome edited breeding tomato line #87-17 with modified function of the tomato’s inheritant glutamate decarboxylase.

The Ministry of Health, Labor and Welfare has ruled that this tomato does not fall under the category of “genetically modified organisms” under the Cartagena Act and can be distributed to customers.

Accordingly, the marketing concept of Sanatec is in Phase 1 is to distribute seedlings, soil conditioners (microorganisms), and fertilizers to home gardeners, and in Phase 2 is to actually begin paid marketing.

https://sanatech-seed.com/en/20201211-1-2/

©Sanatec Seeds Co.

31-3 Will artificial intelligence help us to healthier intestinal microbiomes?

AuB, a Tokyo startup whose president Keita Suzuki is a former member of Japan’s national soccer team, has analyzed the stool of over 700 athletes and analyzed the type, number and composition of their intestinal bacteria, combined with information on eating habits and weight gains. As a result, a new species of Bifidobacterium longum was found to prevail in those athletes  who easily gained muscles and did not gain weight, even though they ate rich meals, https://aub.co.jp/news/aub-001/. Equipment maker Kyocera, which sponsors the soccer club Kyoto Sanga F.C. http://www.sanga-fc.jp  has now teamed up with AuB to develop a toilet-based gas sensor by which stool data of 29 players of the club will be related to their intestinal microbiomes. Using AI, it is expected to correlate odor to the composition of the microbiome and draw conclusions on the management of health and physical performance, 

https://www.kyocera.co.jp/news/2020/0204_fekg.html

©Kyocera

14-4 RIKEN-industry consortium tailors E. coli by synthetic biology to produce 1,3-butadiene from glucose

The team of Yutaro MORI at RIKEN, in collaboration with Yokohama Rubber and ZEON Co., has developed a technology to produce 1,3-butadiene from glucose by recombinant Escherichia coli. Butadiene is currently produced at 12 million t/y worldwide and over 1 million t/y in Japan from petrochemical resources. The recombinant Escherichia coli strain used in this process was bred by synthetic biology technology involving four gene deletions, five gene amplifications and introduction of four foreign genes. In addition to conventional genetic engineering, CRISPR/Cas9, was also used. Using DO–stat fed-batch fermentation, 2.13 ± 0.17 g L−1 1,3-butadiene was produced. 

Y. Mori et al., Nature Communications, https://doi.org/10.1038/s41467-021-22504-6

© RIKEN

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