Faculty Profiles - HIRASAWA TAKASHI

写真a

HIRASAWA TAKASHI

Organization

School of Life Science and Technology Associate Professor

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Degree

博士 (工学) ( 2002.3 )

Research Interests

Metabolic Engineering
Applied Microbiology

Research Areas

Life Science / Applied microbiology
Manufacturing Technology (Mechanical Engineering, Electrical and Electronic Engineering, Chemical Engineering) / Biofunction and bioprocess engineering

Education

Tokyo Institute of Technology Graduate School of Bioscience and Biotechnology

1999.4 - 2002.3

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Tokyo Institute of Technology Graduate School of Bioscience and Biotechnology

1997.4 - 1999.3

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Tokyo University of Science Faculty of Science and Technology Applied Biological Science

1993.4 - 1997.3

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Research History

Institute of Science Tokyo School of Life Science and Technology Associate Professor

2024.10

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Country：Japan

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Tokyo Institute of Technology School of Life Science and Technology Associate Professor

2016.4 - 2024.9

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Tokyo Institute of Technology Graduate School of Bioscience and Biotechnology Associate Professor

2013.9 - 2016.3

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Osaka University Department of Bioinformatic Engineering, Graduate School of Information Science and Technology Assistant Professor

2007.4 - 2013.8

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Keio University Assistant Professor

2005.5 - 2007.3

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Osaka University Graduate School of Engineering Postdoctoral researcher

2002.4 - 2005.4

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Professional Memberships

Society of Genome Microbiology, Japan

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The Society for Biotechnology, Japan

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JAPAN SOCIETY FOR BIOSCIENCE, BIOTECHNOLOGY, AND AGROCHEMISTRY

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Papers

Enhancement of ergothioneine production in Corynebacterium glutamicum by increasing osmotic pressure. Reviewed International journal

Yuno Takahashi, Takashi Hirasawa

Applied microbiology and biotechnology 109 ( 1 ) 255 - 255 2025.12

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Authorship：Last author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

Ergothioneine (EGT), which exhibits strong antioxidant properties, is an amino acid derivative with a betaine structure. Currently, studies have examined EGT import systems and its physiological roles in various organisms. Despite the broad applicability of EGT, industrial production with high productivity has not yet been achieved. In this study, we aimed to develop fermentative production methods for EGT using Corynebacterium glutamicum as a host and successfully achieved the highest yield of EGT (459 mg L-1) reported to date. A cysteine-producing strain C. glutamicum CYS-2, which was constructed in a previous study, was engineered to enhance the biosynthesis of histidine and S-adenosylmethionine, both of which, along with cysteine, are required for EGT production. Additionally, heterologous metabolic pathways for EGT biosynthesis from Mycolicibacterium smegmatis and Methylobacterium pseudosasicola were introduced into the engineered strain, which was designated CHS2. In batch cultivation, the CHS2 strain produced more EGT than the CYS-2 strain harboring the same EGT biosynthesis pathway. Interestingly, batch cultivation of the CHS2 strain under high osmotic pressure conditions prolonged the time for EGT production and increased the intracellular accumulation of EGT. These results suggest that increasing osmotic pressure together with engineering the biosynthesis of cysteine, histidine, and S-adenosylmethionine is an effective strategy for enhancing EGT production in recombinant C. glutamicum harboring heterologous EGT biosynthesis pathways. KEY POINTS: • Ergothioneine production in C. glutamicum was enhanced by metabolic engineering. • Osmotic pressure affects ergothioneine production in engineered C. glutamicum. • Ergothioneine may function as a compatible solute in C. glutamicum.

DOI： 10.1007/s00253-025-13639-3

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Examination of the effect of HOG1 deletion on glucose fermentation in Saccharomyces cerevisiae. Reviewed International coauthorship International journal

Nunthaphan Vikromvarasiri, Ryosuke Mitsui, Takashi Hirasawa, Akihiko Kondo, Tomokazu Shirai

Bioresource technology 434 132788 - 132788 2025.6

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Language：English Publishing type：Research paper (scientific journal)

HOG1 encodes a mitogen-activated protein kinase in Saccharomyces cerevisiae and plays a crucial role in the high osmolarity glycerol pathway during the osmotic stress response. HOG1 loss improves glycerol utilization in yeast; however, its effects on the growth and fermentation profiles during glucose cultivation remain unexplored. Therefore, this study aimed to explore the effects of HOG1 deletion on glucose fermentation. HOG1 deletion led to enhanced glucose utilization and ethanol production by 14.30 % compared to the wild-type strain. Glycerol, acetate, and 2,3-butanediol levels were decreased in the Δhog1 strain. The loss of HOG1 function prevented resistance to high osmotic pressure resulting from high initial glucose fermentation; resistance was restored and enhanced by intermittent feeding. Key genes in central metabolism were deleted to investigate metabolic shifts further. PDC1 and ADH1 deletion induced NADH accumulation and redox imbalance, resulting in GPD2 primarily driving glycerol production. Elucidating the role of HOG1 in glucose fermentation offers novel insights into yeast physiology, with potential applications in biotechnology and industrial processes.

DOI： 10.1016/j.biortech.2025.132788

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Mutations in the ilvN gene mitigate growth inhibitory effect of cysteine in Corynebacterium glutamicum. Reviewed International journal

Kazuho Matsuhisa, Katsuhiro Ogawa, Kento Komata, Takashi Hirasawa

Applied microbiology and biotechnology 109 ( 1 ) 61 - 61 2025.3

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Cysteine, a common amino acid used in food, cosmetic, and pharmaceutical industries, has a growth inhibitory effect. This growth inhibition by cysteine poses a problem, as the production of cysteine using microbial cells results in decreased cell growth and cysteine productivity. The underlying mechanism of growth inhibition by cysteine is unclear. This study aims to understand the mechanism of growth inhibition by cysteine in Corynebacterium glutamicum. To do this, cysteine-resistant mutants of C. glutamicum were isolated based on adaptive laboratory evolution (ALE) and their characteristics were analyzed. Genome resequencing revealed that mutations in the open reading frame of the ilvN gene encoding the regulatory small subunit of acetohydroxyacid synthase (AHAS), which is involved in branched-chain amino acid biosynthesis, were found in ALE cell populations and the isolated cysteine-resistant mutants. The ilvN mutations which are responsible for increased valine production resulted in improved cell growth in the presence of cysteine. Moreover, the addition of valine to the culture medium mitigated growth inhibition by cysteine, whereas the addition of leucine and isoleucine showed a slight mitigation. Additionally, the activity of AHAS from C. glutamicum was inhibited by cysteine, whereas AHAS from the strains carrying ilvN mutations exhibited resistance to cysteine. These results indicate that growth inhibition by cysteine is caused by perturbations in the biosynthesis of branched-chain amino acids, particularly valine in C. glutamicum. Furthermore, the cysteine-resistant mutants obtained by ALE demonstrated enhanced cysteine production as production hosts, suggesting that cysteine resistance is a useful phenotype for cysteine production in C. glutamicum. KEY POINTS: • Cysteine-resistant mutants of C. glutamicum obtained by ALE were analyzed. • Perturbation of valine biosynthesis by cysteine results in growth inhibition in C. glutamicum. • Cysteine resistance is a useful phenotype for cysteine production by C. glutamicum.

DOI： 10.1007/s00253-025-13444-y

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Production of aromatic amino acids and their derivatives by Escherichia coli and Corynebacterium glutamicum. Invited Reviewed International journal

Takashi Hirasawa, Yasuharu Satoh, Daisuke Koma

World journal of microbiology & biotechnology 41 ( 2 ) 65 - 65 2025.2

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Demand for aromatic amino acids (AAAs), such as L-phenylalanine, L-tyrosine, and L-tryptophan, has been increasing as they are used in animal feed and as precursors in the synthesis of industrial and pharmaceutical compounds. These AAAs are biosynthesized through the shikimate pathway in microorganisms and plants, and the reactions in the AAA biosynthesis pathways are strictly regulated at the levels of both gene expression and enzyme activity. Various attempts have been made to produce AAAs and their derivatives using microbial cells and to optimize production. In this review, we summarize the metabolic pathways involved in the biosynthesis of AAAs and their regulation and review recent research on AAA production using industrial bacteria, such as Escherichia coli and Corynebacterium glutamicum. Studies on fermentative production of AAA derivatives, including L-3,4-dihydroxyphenylalanine, tyrosol, and 3-hydroxytyrosol, are also discussed.

DOI： 10.1007/s11274-025-04264-3

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Biotin concentration affects anaplerotic reactions functioning in glutamic acid production in Corynebacterium glutamicum Reviewed

Takako Ochiai, Masaaki Wachi, Takashi Hirasawa

Microbiology 170 ( 10 ) 001507 2024.10

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Authorship：Last author,　Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Microbiology Society

The study investigates the effect of biotin concentration on the role of anaplerotic reactions catalysed by pyruvate carboxylase (PC) and phosphoenolpyruvate carboxylase (PEPC) in glutamic acid production by Corynebacterium glutamicum. C. glutamicum requires biotin for its growth, and its glutamic acid production can be induced by the addition of Tween 40 or penicillin or by biotin limitation. The biotin enzyme PC and the non-biotin enzyme PEPC catalyse two anaplerotic reactions to supply oxaloacetic acid to the TCA cycle in C. glutamicum. Therefore, they are crucial for glutamic acid production in this bacterium. In this study, we investigated the contribution of each anaplerotic reaction to Tween 40- and penicillin-induced glutamic acid production using disruptants of PEPC and PC. In the presence of 20 µg l^–1 biotin, which is sufficient for growth, the PEPC-catalysed anaplerotic reaction mainly contributed to Tween 40- and penicillin-induced glutamic acid production. However, when increasing biotin concentration 10-fold (i.e. 200 µg l^–1), both PC- and PEPC-catalysed reactions could function in glutamic acid production. Western blotting revealed that the amount of biotin-bound PC was reduced by the addition of Tween 40 and penicillin in the presence of 20 µg l^–1. However, these induction treatments did not change the amount of biotin-bound PC in the presence of 200 µg l^–1 biotin. These results indicate that both anaplerotic reactions are functional during glutamic acid production in C. glutamicum and that biotin concentration mainly affects which anaplerotic reactions function during glutamic acid production.

DOI： 10.1099/mic.0.001507

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Metabolic engineering with adaptive laboratory evolution for phenylalanine production by Corynebacterium glutamicum Reviewed

Yukio Tachikawa, Miki Okuno, Takehiko Itoh, Takashi Hirasawa

Journal of Bioscience and Bioengineering 137 ( 5 ) 344 - 353 2024.5

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Authorship：Last author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1016/j.jbiosc.2024.01.006

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Loss of function of Hog1 improves glycerol assimilation in Saccharomyces cerevisiae Reviewed

Masato Sone, Kantawat Navanopparatsakul, Shunsuke Takahashi, Chikara Furusawa, Takashi Hirasawa

World Journal of Microbiology and Biotechnology 39 ( 10 ) 2023.7

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Authorship：Last author,　Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Springer Science and Business Media LLC

Abstract

We previously isolated a mutant of Saccharomyces cerevisiae strain 85_9 whose glycerol assimilation was improved through adaptive laboratory evolution. To investigate the mechanism for this improved glycerol assimilation, genome resequencing of the 85_9 strain was performed, and the mutations in the open reading frame of HOG1, SIR3, SSB2, and KGD2 genes were found. Among these, a frameshift mutation in the HOG1 open reading frame was responsible for the improved glycerol assimilation ability of the 85_9 strain. Moreover, the HOG1 gene disruption improved glycerol assimilation. As HOG1 encodes a mitogen-activated protein kinase (MAPK), which is responsible for the signal transduction cascade in response to osmotic stress, namely the high osmolarity glycerol (HOG) pathway, we investigated the effect of the disruption of PBS2 gene encoding MAPK kinase for Hog1 MAPK on glycerol assimilation, revealing that PBS2 disruption can increase glycerol assimilation. These results indicate that loss of function of Hog1 improves glycerol assimilation in S. cerevisiae. However, single disruption of the SSK2, SSK22 and STE11 genes encoding protein kinases responsible for Pbs2 phosphorylation in the HOG pathway did not increase glycerol assimilation, while their triple disruption partially improved glycerol assimilation in S. cerevisiae. In addition, the HOG1 frameshift mutation did not improve glycerol assimilation in the STL1-overexpressing RIM15 disruptant strain, which was previously constructed with high glycerol assimilation ability. Furthermore, the effectiveness of the HOG1 disruptant as a bioproduction host was validated, indicating that the HOG1 CYB2 double disruptant can produce L-lactic acid from glycerol.

DOI： 10.1007/s11274-023-03696-z

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Other Link： https://link.springer.com/article/10.1007/s11274-023-03696-z/fulltext.html
Ergothioneine production by Corynebacterium glutamicum harboring heterologous biosynthesis pathways Reviewed

Takashi Hirasawa, Yuki Shimoyamada, Yukio Tachikawa, Yasuharu Satoh, Yusuke Kawano, Tohru Dairi, Iwao Ohtsu

Journal of Bioscience and Bioengineering 135 ( 1 ) 25 - 33 2023.1

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Authorship：Lead author,　Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Elsevier BV

DOI： 10.1016/j.jbiosc.2022.10.002

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Adaptive Laboratory Evolution of Microorganisms: Methodology and Application for Bioproduction. Invited Reviewed International journal

Takashi Hirasawa, Tomoya Maeda

Microorganisms 11 ( 1 ) 2022.12

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Authorship：Lead author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

Adaptive laboratory evolution (ALE) is a useful experimental methodology for fundamental scientific research and industrial applications to create microbial cell factories. By using ALE, cells are adapted to the environment that researchers set based on their objectives through the serial transfer of cell populations in batch cultivations or continuous cultures and the fitness of the cells (i.e., cell growth) under such an environment increases. Then, omics analyses of the evolved mutants, including genome sequencing, transcriptome, proteome and metabolome analyses, are performed. It is expected that researchers can understand the evolutionary adaptation processes, and for industrial applications, researchers can create useful microorganisms that exhibit increased carbon source availability, stress tolerance, and production of target compounds based on omics analysis data. In this review article, the methodologies for ALE in microorganisms are introduced. Moreover, the application of ALE for the creation of useful microorganisms as cell factories has also been introduced.

DOI： 10.3390/microorganisms11010092

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Constitutive expression of the global regulator AbrB restores the growth defect of a genome-reduced Bacillus subtilis strain and improves its metabolite production. Reviewed International journal

Junya Yamamoto, Onuma Chumsakul, Yoshihiro Toya, Takuya Morimoto, Shenghao Liu, Kenta Masuda, Yasushi Kageyama, Takashi Hirasawa, Fumio Matsuda, Naotake Ogasawara, Hiroshi Shimizu, Ken-Ichi Yoshida, Taku Oshima, Shu Ishikawa

DNA research : an international journal for rapid publication of reports on genes and genomes 29 ( 3 ) 2022.5

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Partial bacterial genome reduction by genome engineering can improve the productivity of various metabolites, possibly via deletion of non-essential genome regions involved in undesirable metabolic pathways competing with pathways for the desired end products. However, such reduction may cause growth defects. Genome reduction of Bacillus subtilis MGB874 increases the productivity of cellulases and proteases but reduces their growth rate. Here, we show that this growth defect could be restored by silencing redundant or less important genes affecting exponential growth by manipulating the global transcription factor AbrB. Comparative transcriptome analysis revealed that AbrB-regulated genes were upregulated and those involved in central metabolic pathway and synthetic pathways of amino acids and purine/pyrimidine nucleotides were downregulated in MGB874 compared with the wild-type strain, which we speculated were the cause of the growth defects. By constitutively expressing high levels of AbrB, AbrB regulon genes were repressed, while glycolytic flux increased, thereby restoring the growth rate to wild-type levels. This manipulation also enhanced the productivity of metabolites including γ-polyglutamic acid. This study provides the first evidence that undesired features induced by genome reduction can be relieved, at least partly, by manipulating a global transcription regulation system. A similar strategy could be applied to other genome engineering-based challenges aiming toward efficient material production in bacteria.

DOI： 10.1093/dnares/dsac015

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Effectiveness of the Bacillus subtilis genome-reduced strain as an ethanol production host Reviewed

Dita Grinanda, Takashi Hirasawa

Bioscience, Biotechnology, and Biochemistry 86 ( 4 ) 543 - 551 2022.1

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Authorship：Last author,　Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Informa UK Limited

ABSTRACT

We investigated the performance of a genome-reduced strain of Bacillus subtilis MGB874, whose 0.87 Mbp of genomic DNA was cumulatively deleted, as an ethanol production host. A recombinant strain A267_EtOH was constructed by introducing the pdc and adhB genes from Zymomonas mobilis, both of which were expressed from an isopropyl-β-d-1-thiogalactopyranoside-inducible spac promoter, into the A267 strain, a tryptophan prototrophic derivative of the MGB874 with disruption of metabolic pathways for producing lactic acid, acetic acid, and acetoin. Focusing on the stationary phase in fed-batch fermentation, 1.6 g L−1 ethanol was produced by the A267_EtOH strain after 144 h. Moreover, its ethanol production further increased by approximately 3.7-fold (5.9 g L−1) at 80 h through replacing the spac promoter for expressing pdc and adhB genes with the lytR promoter and the yield was about 112%. These results indicate that the MGB874 is an effective host for ethanol production during the stationary phase.

DOI： 10.1093/bbb/zbac017

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Other Link： https://academic.oup.com/bbb/article-pdf/86/4/543/42956449/zbac017.pdf
銅添加によるコリネ型細菌のグルタミン酸生産誘導

平沢敬

バイオサイエンスとインダストリー 80 ( 3 ) 2022

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J-GLOBAL

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Induction of glutamic acid production by copper in Corynebacterium glutamicum Reviewed

Shunsuke Ogata, Takashi Hirasawa

Applied Microbiology and Biotechnology 105 ( 18 ) 6909 - 6920 2021.9

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Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Springer Science and Business Media Deutschland GmbH

DOI： 10.1007/s00253-021-11516-3

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13C-metabolic flux analysis in glycerol-assimilating strains of Saccharomyces cerevisiae. Reviewed

The Journal of General and Applied Microbiology 67 ( 4 ) 142 - 149 2021.5

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Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Microbiology Research Foundation

Glycerol is an attractive raw material for the production of useful chemicals using microbial cells. We previously identified metabolic engineering targets for the improvement of glycerol assimilation ability in Saccharomyces cerevisiae based on adaptive laboratory evolution (ALE) and transcriptome analysis of the evolved cells. We also successfully improved glycerol assimilation ability by the disruption of the RIM15 gene encoding a Greatwall protein kinase together with overexpression of the STL1 gene encoding the glycerol/H⁺ symporter. To understand glycerol assimilation metabolism in the evolved glycerol-assimilating strains and STL1-overexpressing RIM15 disruptant, we performed metabolic flux analysis using ¹³C-labeled glycerol. Significant differences in metabolic flux distributions between the strains obtained from the culture after 35 and 85 generations in ALE were not found, indicating that metabolic flux changes might occur in the early phase of ALE (i.e., before 35 generations at least). Similarly, metabolic flux distribution was not significantly changed by RIM15 gene disruption. However, fluxes for the lower part of glycolysis and the TCA cycle were larger and, as a result, flux for the pentose phosphate pathway was smaller in the STL1-overexpressing RIM15 disruptant than in the strain obtained from the culture after 85 generations in ALE. It could be effective to increase flux for the pentose phosphate pathway to improve the glycerol assimilation ability in S. cerevisiae.

DOI： 10.2323/jgam.2020.10.001

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Requirement of the LtsA Protein for Formation of the Mycolic Acid-Containing Layer on the Cell Surface of Corynebacterium glutamicum. Invited Reviewed

Yutaro Kumagai, Takashi Hirasawa, Masaaki Wachi

Microorganisms 2021.2

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The ltsA gene of Corynebacterium glutamicum encodes a purF-type glutamine-dependent amidotransferase, and mutations in this gene result in increased susceptibility to lysozyme. Recently, it was shown that the LtsA protein catalyzes the amidation of diaminopimelate residues in the lipid intermediates of peptidoglycan biosynthesis. In this study, intracellular localization of wild-type and mutant LtsA proteins fused with green fluorescent protein (GFP) was investigated. The GFP-fused wild-type LtsA protein showed a peripheral localization pattern characteristic of membrane-associated proteins. The GFP-fusions with a mutation in the N-terminal domain of LtsA, which is necessary for the glutamine amido transfer reaction, exhibited a similar localization to the wild type, whereas those with a mutation or a truncation in the C-terminal domain, which is not conserved among the purF-type glutamine-dependent amidotransferases, did not. These results suggest that the C-terminal domain is required for peripheral localization. Differential staining of cell wall structures with fluorescent dyes revealed that formation of the mycolic acid-containing layer at the cell division planes was affected in the ltsA mutant cells. This was also confirmed by observation that bulge formation was induced at the cell division planes in the ltsA mutant cells upon lysozyme treatment. These results suggest that the LtsA protein function is required for the formation of a mycolic acid-containing layer at the cell division planes and that this impairment results in increased susceptibility to lysozyme.

DOI： 10.3390/microorganisms9020409

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続・生物工学基礎講座バイオよもやま話コリネ型細菌Corynebacterium glutamicum-グルタミン酸生産の基礎と有用物質生産への応用-

平沢敬

生物工学会誌 99 ( 1 ) 2021

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Growth promotion in Corynebacterium glutamicum by overexpression of the NCgl2986 gene encoding a protein homologous to peptidoglycan amidases Reviewed

Mia Fitria Utami, Yoshihiko Matsuda, Ayako Takada, Noritaka Iwai, Takashi Hirasawa, Masaaki Wachi

The Journal of General and Applied Microbiology 66 ( 1 ) 1 - 7 2020

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Language：English Publishing type：Research paper (scientific journal) Publisher：Microbiology Research Foundation

DOI： 10.2323/jgam.2019.03.002

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Enhanced L-cysteine production by overexpressing potential L-cysteine exporter genes in an L-cysteine-producing recombinant strain of Corynebacterium glutamicum Reviewed

Bioscience, Biotechnology, and Biochemistry 2019

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DOI： 10.1080/09168451.2019.1659715

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Other Link： http://orcid.org/0000-0002-5183-2953
L-Cysteine production by metabolically engineered Corynebacterium glutamicum Reviewed

Mariko Kondoh, Takashi Hirasawa

Applied Microbiology and Biotechnology 2019

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Authorship：Last author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1007/S00253-019-09663-9

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Other Link： http://orcid.org/0000-0002-5183-2953
Identification of metabolic engineering targets for improving glycerol assimilation ability of Saccharomyces cerevisiae based on adaptive laboratory evolution and transcriptome analysis Reviewed

Journal of Bioscience and Bioengineering 2019

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DOI： 10.1016/J.JBIOSC.2019.02.001

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Other Link： http://orcid.org/0000-0002-5183-2953
Integrated Analysis of the Transcriptome and Metabolome of Corynebacterium glutamicum during Penicillin-Induced Glutamic Acid Production Reviewed

Takashi Hirasawa, Masaki Saito, Katsunori Yoshikawa, Chikara Furusawa, Hiroshi Shmizu

Biotechnology Journal 13 ( 5 ) 2018.5

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1002/biot.201700612

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Other Link： http://orcid.org/0000-0002-5183-2953
Omics-integrated approach for metabolic state analysis of microbial processes

Hiroshi Shimizu, Chikara Furusawa, Takashi Hirasawa, Katsunori Yoshikawa, Yoshihiro Toya, Tomokazu Shirai, Fumio Matsuda

Applied Bioengineering: Innovations and Future Directions 213 - 236 2017.1

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Language：English Publishing type：Part of collection (book) Publisher：wiley

DOI： 10.1002/9783527800599.ch7

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Glutamate Fermentation-2: Mechanism of L-Glutamate Overproduction in Corynebacterium glutamicum Reviewed

Takashi Hirasawa, Masaaki Wachi

AMINO ACID FERMENTATION 159 57 - 72 2017

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1007/10_2016_26

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Other Link： http://orcid.org/0000-0002-5183-2953
Recent advances in amino acid production by microbial cells Reviewed

Takashi Hirasawa, Hiroshi Shimizu

CURRENT OPINION IN BIOTECHNOLOGY 42 133 - 146 2016.12

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Language：English

DOI： 10.1016/j.copbio.2016.04.017

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Glutamic acid fermentation: Discovery of glutamic acid-producing microorganisms, analysis of the production mechanism, metabolic engineering, and industrial production process Reviewed

Takashi Hirasawa, Hiroshi Shimizu

Industrial Biotechnology: Products and Processes 339 - 360 2016.11

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Language：English Publishing type：Part of collection (book) Publisher：Wiley-VCH Verlag

DOI： 10.1002/9783527807833

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Enhancement of 1,5-diaminopentane production in a recombinant strain of Corynebacterium glutamicum by Tween 40 addition Reviewed

Yuta Matsushima, Takashi Hirasawa, Hiroshi Shimizu

JOURNAL OF GENERAL AND APPLIED MICROBIOLOGY 62 ( 1 ) 42 - 45 2016

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.2323/jgam.62.42

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Other Link： http://orcid.org/0000-0002-5183-2953
Enhanced dipicolinic acid production during the stationary phase in Bacillus subtilis by blocking acetoin synthesis Reviewed

Yoshihiro Toya, Takashi Hirasawa, Shu Ishikawa, Onuma Chumsakul, Takuya Morimoto, Shenghao Liu, Kenta Masuda, Yasushi Kageyama, Katsuya Ozaki, Naotake Ogasawara, Hiroshi Shimizu

BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 79 ( 12 ) 2073 - 2080 2015.12

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DOI： 10.1080/09168451.2015.1060843

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Phenotypic convergence in bacterial adaptive evolution to ethanol stress Reviewed

Takaaki Horinouchi, Shingo Suzuki, Takashi Hirasawa, Naoaki Ono, Tetsuya Yomo, Hiroshi Shimizu, Chikara Furusawa

BMC EVOLUTIONARY BIOLOGY 15 2015.9

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1186/s12862-015-0454-6

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Effect of malic enzyme on ethanol production by Synechocystis sp PCC 6803 Reviewed

Katsunori Yoshikawa, Takashi Hirasawa, Hiroshi Shimizu

JOURNAL OF BIOSCIENCE AND BIOENGINEERING 119 ( 1 ) 82 - 84 2015.1

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1016/j.jbiosc.2014.06.001

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Characterization of a Corynebacterium glutamicum dnaB mutant that shows temperature-sensitive growth and mini-cell formation Reviewed

Makoto Uchida, Takashi Hirasawa, Masaaki Wachi

ARCHIVES OF MICROBIOLOGY 196 ( 12 ) 871 - 879 2014.12

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1007/s00203-014-1026-7

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Integrated Metabolic Flux and Omics Analysis of Synechocystis sp PCC 6803 under Mixotrophic and Photoheterotrophic Conditions Reviewed

Tsubasa Nakajima, Shuichi Kajihata, Katsunori Yoshikawa, Fumio Matsuda, Chikara Furusawa, Takashi Hirasawa, Hiroshi Shimizu

PLANT AND CELL PHYSIOLOGY 55 ( 9 ) 1605 - 1612 2014.9

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DOI： 10.1093/pcp/pcu091

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C-13-metabolic flux analysis in heterologous cellulase production by Bacillus subtilis genome-reduced strain Reviewed

Yoshihiro Toya, Takashi Hirasawa, Takuya Morimoto, Kenta Masuda, Yasushi Kageyama, Katsuya Ozaki, Naotake Ogasawara, Hiroshi Shimizu

JOURNAL OF BIOTECHNOLOGY 179 42 - 49 2014.6

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1016/j.jbiotec.2014.03.025

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Increased 3-hydroxypropionic acid production from glycerol, by modification of central metabolism in Escherichia coli Reviewed

Kento Tokuyama, Satoshi Ohno, Katsunori Yoshikawa, Takashi Hirasawa, Shotaro Tanaka, Chikara Furusawa, Hiroshi Shimizu

MICROBIAL CELL FACTORIES 13 2014.5

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1186/1475-2859-13-64

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Glutamic Acid Reviewed

Takashi Hirasawa, Hiroshi Shimizu

Bioprocessing of Renewable Resources to Commodity Bioproducts 473 - 495 2014.4

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DOI： 10.1002/9781118845394.ch17

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Potential of a Saccharomyces cerevisiae recombinant strain lacking ethanol and glycerol biosynthesis pathways in efficient anaerobic bioproduction Reviewed

Takashi Hirasawa, Yoshihiro Ida, Chikara Furusawa, Hiroshi Shimizu

BIOENGINEERED 5 ( 2 ) 123 - 128 2014.3

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DOI： 10.4161/bioe.26569

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Metabolic engineering of Saccharomyces cerevisiae to improve succinic acid production based on metabolic profiling Reviewed

Yuma Ito, Takashi Hirasawa, Hiroshi Shimizu

BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 78 ( 1 ) 151 - 159 2014.1

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DOI： 10.1080/09168451.2014.877816

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Enhanced acetic acid and succinic acid production under microaerobic conditions by Corynebacterium glutamicum harboring Escherichia coli transhydrogenase gene pntAB Reviewed

Yuto Yamauchi, Takashi Hirasawa, Masato Nishii, Chikara Furusawa, Hiroshi Shimizu

JOURNAL OF GENERAL AND APPLIED MICROBIOLOGY 60 ( 3 ) 112 - 118 2014

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DOI： 10.2323/jgam.60.112

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Genome-wide identification of the targets for genetic manipulation to improve l-lactate production by Saccharomyces cerevisiae by using a single-gene deletion strain collection Reviewed

Takashi Hirasawa, Masakado Takekuni, Katsunori Yoshikawa, Aki Ookubo, Chikara Furusawa, Hiroshi Shimizu

Journal of Biotechnology 168 ( 2 ) 185 - 193 2013.10

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DOI： 10.1016/j.jbiotec.2013.04.020

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Design of superior cell factories based on systems wide omics analysis Reviewed

Katsunori Yoshikawa, Chikara Furusawa, Takashi Hirasawa, Hiroshi Shimizu

Systems Metabolic Engineering 57 - 81 2013.8

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DOI： 10.1007/978-94-007-4534-6_3

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Utilization of Saccharomyces cerevisiae recombinant strain incapable of both ethanol and glycerol biosynthesis for anaerobic bioproduction Reviewed

Yoshihiro Ida, Takashi Hirasawa, Chikara Furusawa, Hiroshi Shimizu

Applied Microbiology and Biotechnology 97 ( 11 ) 4811 - 4819 2013.6

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DOI： 10.1007/s00253-013-4760-x

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Integrated transcriptomic and metabolomic analysis of the central metabolism of Synechocystis sp PCC 6803 under different trophic conditions Reviewed

Katsunori Yoshikawa, Takashi Hirasawa, Kenichi Ogawa, Yuki Hidaka, Tsubasa Nakajima, Chikara Furusawa, Hiroshi Shimizu

BIOTECHNOLOGY JOURNAL 8 ( 5 ) 571 - 580 2013.5

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DOI： 10.1002/biot.201200235

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Systems Metabolic Engineering: The Creation of Microbial Cell Factories by Rational Metabolic Design and Evolution Reviewed

Chikara Furusawa, Takaaki Horinouchi, Takashi Hirasawa, Hiroshi Shimizu

FUTURE TRENDS IN BIOTECHNOLOGY 131 1 - 23 2013

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DOI： 10.1007/10_2012_137

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Investigating the effects of perturbations to pgi and eno gene expression on central carbon metabolism in Escherichia coli using C-13 metabolic flux analysis Reviewed

Yuki Usui, Takashi Hirasawa, Chikara Furusawa, Tomokazu Shirai, Natsuko Yamamoto, Hirotada Mori, Hiroshi Shimizu

MICROBIAL CELL FACTORIES 11 2012.6

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DOI： 10.1186/1475-2859-11-87

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Understanding the mechanism of heat stress tolerance caused by high trehalose accumulation in Saccharomyces cerevisiae using DNA microarray Reviewed

Siraje Arif Mahmud, Takashi Hirasawa, Chikara Furusawa, Katsunori Yoshikawa, Hiroshi Shimizu

JOURNAL OF BIOSCIENCE AND BIOENGINEERING 113 ( 4 ) 526 - 528 2012.4

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DOI： 10.1016/j.jbiosc.2011.11.028

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Stable disruption of ethanol production by deletion of the genes encoding alcohol dehydrogenase isozymes in Saccharomyces cerevisiae Reviewed

Yoshihiro Ida, Chikara Furusawa, Takashi Hirasawa, Hiroshi Shimizu

JOURNAL OF BIOSCIENCE AND BIOENGINEERING 113 ( 2 ) 192 - 195 2012.2

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DOI： 10.1016/j.jbiosc.2011.09.019

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Molecular mechanisms and metabolic engineering of glutamate overproduction in Corynebacterium glutamicum. Reviewed International journal

Hirasawa Takashi, Kim Jongpill, Shirai Tomokazu, Furusawa Chikara, Shimizu Hiroshi

Sub-cellular biochemistry 64 261 - 81 2012

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Glutamate is a commercially important chemical. It is used as a flavor enhancer and is a major raw material for producing industrially useful chemicals. A coryneform bacterium, Corynebacterium glutamicum, was isolated in 1956 by Japanese researchers as a glutamate-overproducing bacterium and since then, remarkable progress in glutamate production has been made using this microorganism. Currently, the global market for glutamate is over 2.5 million tons per year. Glutamate overproduction by C. glutamicum is induced by specific treatments-biotin limitation, addition of fatty acid ester surfactants such as Tween 40, and addition of β-lactam antibiotics such as penicillin. Molecular biology and metabolic engineering studies on glutamate overproduction have revealed that metabolic flow is significantly altered by these treatments. These studies have also provided insight into the molecular mechanisms underlying these changes. In this chapter, we review our current understanding of the molecular mechanisms of glutamate overproduction in C. glutamicum, and we discuss the advances made by metabolic engineering of this microorganism.

DOI： 10.1007/978-94-007-5055-5_13

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Improving protein secretion of a transglutaminase-secreting Corynebacterium glutamicum recombinant strain on the basis of C-13 metabolic flux analysis Reviewed

Motoki Umakoshi, Takashi Hirasawa, Chikara Furusawa, Yasuhiro Takenaka, Yoshimi Kikuchi, Hiroshi Shimizu

JOURNAL OF BIOSCIENCE AND BIOENGINEERING 112 ( 6 ) 595 - 601 2011.12

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DOI： 10.1016/j.jbiosc.2011.08.011

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Reconstruction and verification of a genome-scale metabolic model for Synechocystis sp PCC6803 Reviewed

Katsunori Yoshikawa, Yuta Kojima, Tsubasa Nakajima, Chikara Furusawa, Takashi Hirasawa, Hiroshi Shimizu

APPLIED MICROBIOLOGY AND BIOTECHNOLOGY 92 ( 2 ) 347 - 358 2011.10

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DOI： 10.1007/s00253-011-3559-x

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Investigation of phosphorylation status of OdhI protein during penicillin- and Tween 40-triggered glutamate overproduction by Corynebacterium glutamicum Reviewed

Jongpill Kim, Takashi Hirasawa, Masaki Saito, Chikara Furusawa, Hiroshi Shimizu

APPLIED MICROBIOLOGY AND BIOTECHNOLOGY 91 ( 1 ) 143 - 151 2011.7

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DOI： 10.1007/s00253-011-3275-6

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Comprehensive phenotypic analysis of single-gene deletion and overexpression strains of Saccharomyces cerevisiae Reviewed

Katsunori Yoshikawa, Tadamasa Tanaka, Yoshihiro Ida, Chikara Furusawa, Takashi Hirasawa, Hiroshi Shimizu

YEAST 28 ( 5 ) 349 - 361 2011.5

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DOI： 10.1002/yea.1843

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Genome-wide expression analysis of Saccharomyces pastorianus orthologous genes using oligonucleotide microarrays Reviewed

Takaaki Horinouchi, Katsunori Yoshikawa, Risa Kawaide, Chikara Furusawa, Yoshihiro Nakao, Takashi Hirasawa, Hiroshi Shimizu

JOURNAL OF BIOSCIENCE AND BIOENGINEERING 110 ( 5 ) 602 - 607 2010.11

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DOI： 10.1016/j.jbiosc.2010.05.011

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Transcriptome analysis of parallel-evolved Escherichia coli strains under ethanol stress Reviewed

Takaaki Horinouchi, Kuniyasu Tamaoka, Chikara Furusawa, Naoaki Ono, Shingo Suzuki, Takashi Hirasawa, Tetsuya Yomo, Hiroshi Shimizu

BMC GENOMICS 11 2010.10

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DOI： 10.1186/1471-2164-11-579

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13C-Metabolic Flux Analysis for Batch Culture of Escherichia coli and Its pyk and pgi Gene Knockout Mutants based on Mass Isotopomer Distribution of Intracellular Metabolites

TOYA Yoshihiro, ISHII Nobuyoshi, NAKAHIGASHI Kenji, HIRASAWA Takashi, SOGA Tomoyoshi, TOMITA Masaru, SHIMIZU Kazuyuki

Biotechnol Prog 26 ( 4 ) 975-992 2010.7

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Saccharomyces cerevisiae and DNA microarray analyses: what did we learn from it for a better understanding and exploitation of yeast biotechnology? Reviewed

Takashi Hirasawa, Chikara Furusawa, Hiroshi Shimizu

APPLIED MICROBIOLOGY AND BIOTECHNOLOGY 87 ( 2 ) 391 - 400 2010.6

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DOI： 10.1007/s00253-010-2582-7

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Requirement of de novo synthesis of the OdhI protein in penicillin-induced glutamate production by Corynebacterium glutamicum Reviewed

Jongpill Kim, Hirohisa Fukuda, Takashi Hirasawa, Keisuke Nagahisa, Kazuo Nagai, Masaaki Wachi, Hiroshi Shimizu

APPLIED MICROBIOLOGY AND BIOTECHNOLOGY 86 ( 3 ) 911 - 920 2010.4

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DOI： 10.1007/s00253-009-2360-6

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Differential importance of trehalose accumulation in Saccharomyces cerevisiae in response to various environmental stresses Reviewed

Siraje Arif Mahmud, Takashi Hirasawa, Hiroshi Shimizu

JOURNAL OF BIOSCIENCE AND BIOENGINEERING 109 ( 3 ) 262 - 266 2010.3

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DOI： 10.1016/j.jbiosc.2009.08.500

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Relationship between noise characteristics in protein expressions and regulatory structures of amino acid biosynthesis pathways Reviewed

T. Yamada, J. Ou, C. Furusawa, T. Hirasawa, T. Yomo, H. Shimizu

IET SYSTEMS BIOLOGY 4 ( 1 ) 82 - 89 2010.1

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DOI： 10.1049/iet-syb.2008.0158

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Investigating the effectiveness of DNA microarray analysis for identifying the genes involved in l-lactate production by Saccharomyces cerevisiae Reviewed

Takashi Hirasawa, Aki Ookubo, Katsunori Yoshikawa, Keisuke Nagahisa, Chikara Furusawa, Hideki Sawai, Hiroshi Shimizu

APPLIED MICROBIOLOGY AND BIOTECHNOLOGY 84 ( 6 ) 1149 - 1159 2009.10

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DOI： 10.1007/s00253-009-2209-z

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Analysis of adaptation to high ethanol concentration in Saccharomyces cerevisiae using DNA microarray Reviewed

Thai Nho Dinh, Keisuke Nagahisa, Katsunori Yoshikawa, Takashi Hirasawa, Chikara Furusawa, Hiroshi Shimizu

BIOPROCESS AND BIOSYSTEMS ENGINEERING 32 ( 5 ) 681 - 688 2009.8

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DOI： 10.1007/s00449-008-0292-7

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Development and experimental verification of a genome-scale metabolic model for Corynebacterium glutamicum Reviewed

Yohei Shinfuku, Natee Sorpitiporn, Masahiro Sono, Chikara Furusawa, Takashi Hirasawa, Hiroshi Shimizu

MICROBIAL CELL FACTORIES 8 2009.8

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DOI： 10.1186/1475-2859-8-43

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Proteomic analysis of responses to osmotic stress in laboratory and sake-brewing strains of Saccharomyces cerevisiae Reviewed

Takashi Hirasawa, Kazuyuki Yamada, Keisuke Nagahisa, Thai Nho Dinh, Chikara Furusawa, Yoshio Katakura, Suteaki Shioya, Hiroshi Shimizu

PROCESS BIOCHEMISTRY 44 ( 6 ) 647 - 653 2009.6

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DOI： 10.1016/j.procbio.2009.02.004

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Comprehensive phenotypic analysis for identification of genes affecting growth under ethanol stress in Saccharomyces cerevisiae Reviewed

Katsunori Yoshikawa, Tadamasa Tanaka, Chikara Furusawa, Keisuke Nagahisa, Takashi Hirasawa, Hiroshi Shimizu

FEMS YEAST RESEARCH 9 ( 1 ) 32 - 44 2009.2

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DOI： 10.1111/j.1567-1364.2008.00456.x

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Effect of trehalose accumulation on response to saline stress in Saccharomyces cerevisiae Reviewed

Siraje Arif Mahmud, Keisuke Nagahisa, Takashi Hirasawa, Katsunori Yoshikawa, Kengo Ashitani, Hiroshi Shimizu

YEAST 26 ( 1 ) 17 - 30 2009.1

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DOI： 10.1002/yea.1646

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Effect of odhA overexpression and odhA antisense RNA expression on Tween-40-triggered glutamate production by Corynebacterium glutamicum. Reviewed

Kim J, Hirasawa T, Sato Y, Nagahisa K, Furusawa C, Shimizu H

Applied microbiology and biotechnology 81 ( 6 ) 1097 - 1106 2009.1

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DOI： 10.1007/s00253-008-1743-4

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Genome-wide Analysis of the Effects of Location and Number of Stress Response Elements on Gene Expression in Saccharomyces cerevisiae Reviewed

Katsunori Yoshikawa, Chikara Furusawa, Takashi Hirasawa, Hiroshi Shimizu

JOURNAL OF BIOSCIENCE AND BIOENGINEERING 106 ( 5 ) 507 - 510 2008.11

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DOI： 10.1263/jbb.106.507

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Improvement of L-Lactate Production by CYB2 Gene Disruption in a Recombinant Saccharomyces cerevisiae Strain under Low pH Condition Reviewed

Aki Ookubo, Takashi Hirasawa, Katsunori Yoshikawa, Keisuke Nagahisa, Chikara Furusawa, Hiroshi Shimizu

BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 72 ( 11 ) 3063 - 3066 2008.11

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DOI： 10.1271/bbb.80493

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Comprehensive phenotypic analysis of yeast under ethanol stress condition Reviewed

Katsunori Yoshikawa, Tadamasa Tanaka, Chikara Furusawa, Keisuke Nagahisa, Takashi Hirasawa, Hiroshi Shimizu

JOURNAL OF BIOTECHNOLOGY 136 S111 - S111 2008.10

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DOI： 10.1016/j.jbiotec.2008.07.014

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Distinct roles of two anaplerotic pathways in glutamate production induced by biotin limitation in Corynebacterium glutamicum Reviewed

Hiroki Sato, Keita Orishimo, Tomokazu Shirai, Takashi Hirasawa, Keisuke Nagahisa, Hiroshi Shimizu, Masaaki Wachi

JOURNAL OF BIOSCIENCE AND BIOENGINEERING 106 ( 1 ) 51 - 58 2008.7

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DOI： 10.1263/jbb.106.51

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Adaptation of Saccharomyces cerevisiae Cells to High Ethanol Concentration and Changes in Fatty Acid Composition of Membrane and Cell Size Reviewed

Thai Nho Dinh, Keisuke Nagahisa, Takashi Hirasawa, Chikara Furusawa, Hiroshi Shimizu

PLOS ONE 3 ( 7 ) 2008.7

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DOI： 10.1371/journal.pone.0002623

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Dynamic change in promoter activation during lysine biosynthesis in Escherichia coli cells Reviewed

Jianhong Ou, Tadashi Yamada, Keisuke Nagahisa, Takashi Hirasawa, Chikara Furusawa, Tetsuya Yomo, Hiroshi Shimizu

MOLECULAR BIOSYSTEMS 4 ( 2 ) 128 - 134 2008

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DOI： 10.1039/b711035a

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Metabolic flux balance analysis of an industrially useful microorganism corynebacerium glutamicum by a genome-scale reconstructed model

Hiroshi Shimizu, Yohei Shinfuku, Masahiro Sono, Chikara Furusawa, Takashi Hirasawa

3rd International ICST Conference on Bio-Inspired Models of Network, Information and Computing Systems, BIONETICS 2008 2008

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DOI： 10.4108/icst.bionetics2008.4704

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Identification of target genes conferring ethanol stress tolerance to Saccharomyces cerevisiae based on DNA microarray data analysis Reviewed

Takashi Hirasawa, Katsunori Yoshikawa, Yuki Nakakura, Keisuke Nagahisa, Chikara Furusawa, Yoshio Katakura, Hiroshi Shimizu, Suteaki Shioya

JOURNAL OF BIOTECHNOLOGY 131 ( 1 ) 34 - 44 2007.8

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DOI： 10.1016/j.jbiotec.2007.05.010

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Metabolic pathway recruiting through genomic data analysis for industrial application of Saccharomyces cerevisiae Reviewed

Suteaki Shioya, Hiroshi Shimizu, Takashi Hirasawa, Keisuke Nagahisa, Chikara Furusawa, Gaurav Pandey, Yoshio Katakura

BIOCHEMICAL ENGINEERING JOURNAL 36 ( 1 ) 28 - 37 2007.8

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DOI： 10.1016/j.bej.2006.06.012

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Direct measurement of isotopomer of intracellular metabolites using capillary electrophoresis time-of-flight mass spectrometry for efficient metabolic flux analysis Reviewed

Yoshihiro Toya, Nobuyoshi Ishii, Takashi Hirasawa, Miki Naba, Kenta Hirai, Kaori Sugawara, Saori Igarashi, Kazuyuki Shimizu, Masaru Tomita, Tomoyoshi Soga

JOURNAL OF CHROMATOGRAPHY A 1159 ( 1-2 ) 134 - 141 2007.8

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DOI： 10.1016/j.chroma.2007.04.011

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Extracting the hidden features in saline osmotic tolerance in Saccharomyces cerevisiae from DNA microarray data using the self-organizing map: biosynthesis of amino acids Reviewed

Gaurav Pandey, Katsunori Yoshikawa, Takashi Hirasawa, Keisuke Nagahisa, Yoshio Katakura, Chikara Furusawa, Hiroshi Shimizu, Suteaki Shioya

APPLIED MICROBIOLOGY AND BIOTECHNOLOGY 75 ( 2 ) 415 - 426 2007.5

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DOI： 10.1007/s00253-007-0837-8

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Multiple high-throughput analyses monitor the response of E-coli to perturbations Reviewed

Nobuyoshi Ishii, Kenji Nakahigashi, Tomoya Baba, Martin Robert, Tomoyoshi Soga, Akio Kanai, Takashi Hirasawa, Miki Naba, Kenta Hirai, Aminul Hoque, Pei Yee Ho, Yuji Kakazu, Kaori Sugawara, Saori Igarashi, Satoshi Harada, Takeshi Masuda, Naoyuki Sugiyama, Takashi Togashi, Miki Hasegawa, Yuki Takai, Katsuyuki Yugi, Kazuharu Arakawa, Nayuta Iwata, Yoshihiro Toya, Yoichi Nakayama, Takaaki Nishioka, Kazuyuki Shimizu, Hirotada Mori, Masaru Tomita

SCIENCE 316 ( 5824 ) 593 - 597 2007.4

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DOI： 10.1126/science.1132067

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Inverse metabolic engineering by integration of multiple omics analyses

Hiroshi Shimizu, Takashi Hirasawa, Katsunori Yoshikawa, Yuki Nakakura, Keisuke Nagahisa, Chikara Furusawa, Yoshio Katakura, Suteaki Shioya

IFAC Proceedings Volumes (IFAC-PapersOnline) 10 19 - 24 2007

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DOI： 10.3182/20070604-3-mx-2914.00005

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Production of glutamate and glutamate-related amino acids: Molecular mechanism analysis and metabolic engineering Invited Reviewed

Hiroshi Shimizu, Takashi Hirasawa

Microbiology Monograph 5 1 - 38 2007

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Comparison of transcriptional responses to osmotic stresses induced by NaCl and sorbitol additions in Saccharomyces cerevisiae using DNA microarray Reviewed

Takashi Hirasawa, Kengo Ashitani, Katsunori Yoshikawa, Keisuke Nagahisa, Chikara Furusawa, Yoshio Katakura, Hiroshi Shimizu, Suteaki Shioya

JOURNAL OF BIOSCIENCE AND BIOENGINEERING 102 ( 6 ) 568 - 571 2006.12

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DOI： 10.1263/jbb.102.568

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Comparative analysis of transcriptional responses to saline stress in the laboratory and brewing strains of Saccharomyces cerevisiae with DNA microarray Reviewed

T Hirasawa, Y Nakakura, K Yoshikawa, K Ashitani, K Nagahisa, C Furusawa, Y Katakura, H Shimizu, S Shioya

APPLIED MICROBIOLOGY AND BIOTECHNOLOGY 70 ( 3 ) 346 - 357 2006.4

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DOI： 10.1007/s00253-005-0192-6

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Fluorescent phospholipid analogs as microscopic probes for detection of the mycolic acid-containing layer in Corynebacterium glutamicum: Detecting alterations in the mycolic acid-containing layer following ethambutol treatment Reviewed

Y Kumagai, T Hirasawa, K Hayakawa, K Nagai, M Wachi

BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 69 ( 11 ) 2051 - 2056 2005.11

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DOI： 10.1271/bbb.69.2051

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DNA microarray analysis on Saccharomyces cerevisiae under high carbon dioxide concentration in fermentation process Reviewed

K Nagahisa, T Nakajima, K Yoshikawa, T Hirasawa, Y Katakura, C Furusawa, S Shioya, H Shimizu

BIOTECHNOLOGY AND BIOPROCESS ENGINEERING 10 ( 5 ) 451 - 461 2005.9

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Analysis of responses of complex bionetworks to changes in environmental conditions Reviewed

H Shimizu, T Hirasawa, K Nagahisa, S Shioya

BIOLOGICALLY INSPIRED APPROACHES TO ADVANCED INFORMATION TECHNOLOGY 3141 13 - 27 2004

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A Corynebacterium glutamicum rnhA recG double mutant showing lysozymesensitivity, temperature-sensitive growth, and UV-sensitivity Reviewed

T Hirasawa, Y Kumagai, K Nagai, M Wachi

BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 67 ( 11 ) 2416 - 2424 2003.11

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DOI： 10.1271/bbb.67.2416

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kdsA mutations affect FtsZ-ring formation in Escherichia coli K-12 Reviewed

H Fujishima, A Nishimura, M Wachi, H Takagi, T Hirasawa, H Teraoka, K Nishimori, T Kawabata, K Nishikawa, K Nagai

MICROBIOLOGY-SGM 148 103 - 112 2002.1

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DOI： 10.1099/00221287-148-1-103

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L-glutamate production by lysozyme-sensitive Corynebacterium glutamicum ItsA mutant strains Reviewed

Takashi Hirasawa, Masaaki Wachi, Kazuo Nagai

BMC Biotechnology 1 9 2001.10

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DOI： 10.1186/1472-6750-1-9

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A mutation in the Corynebacterium glutamicum ItsA gene causes susceptibility to lysozyme, temperature-sensitive growth, and L-glutamate production Reviewed

T Hirasawa, M Wachi, K Nagai

JOURNAL OF BACTERIOLOGY 182 ( 10 ) 2696 - 2701 2000.5

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DOI： 10.1128/JB.182.10.2696-2701.2000

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fcsA29 mutation is an allele of polA gene of Escherichia coli Reviewed

K Nagano, M Wachi, A Takada, F Takaku, T Hirasawa, K Nagai

BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 63 ( 2 ) 427 - 429 1999.2

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DOI： 10.1271/bbb.63.427

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Books

バイオテクノロジーシリーズ微生物を活用した有用物質の製造技術

平沢敬（ Role： Contributor第7章食品素材の生産 1. コリネ型細菌Corynebacterium glutamicumによるアミノ酸の発酵生産：L-グルタミン酸の直接発酵とアミノ酸生産株の育種）

シーエムシー出版 2023.5

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ベーシックマスター生化学

平沢敬（ Role： Contributor第9章クエン酸回路と電子伝達系）

オーム社 2008

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Presentations

出芽酵母を宿主としたcis, cis-ムコン酸の生産

小圷玲子, 平沢敬

日本農芸化学会2025年度大会 2025.3

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Event date： 2025.3

Language：Japanese Presentation type：Poster presentation

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コリネ型細菌Corynebacterium glutamicumにおけるodhI遺伝子の発現量増加とグルタミン酸生産の関係

宮内翼, 平沢敬

第76回日本生物工学会大会 2024.9

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Language：Japanese Presentation type：Oral presentation (general)

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コリネ型細菌の適応実験室進化による人工代謝経路の増強とメカニズムの解明

井口元太, 山本啓介, 平沢敬

第76回日本生物工学会大会 2024.9

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Event date： 2024.9

Language：Japanese Presentation type：Oral presentation (general)

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出芽酵母におけるCrabtree効果の抑制に関する研究

渡邉莉歩, 平沢敬

第22回微生物研究会 2024.11

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コリネ型細菌Corynebacterium glutamicumによるイソプレン生産に向けた代謝改変

齋藤拳斗, 平沢敬

日本農芸化学会関東支部2024年度大会 2024.8

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出芽酵母の代謝改変によるcis,cis-ムコン酸の生産

小圷玲子, 平沢敬

第22回微生物研究会 2024.11

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コリネ型細菌のO-アセチルホモセリン生産株の育種

小又健人, 平沢敬

第22回微生物研究会 2024.11

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Awards

日本生物工学会第１９回生物工学論文賞

2011.9 日本生物工学会 Differential importance of trehalose accumulation in Saccharomyces cerevisiae in response to various environmental stresses

Siraje Arif Mahmud, 平沢敬, 清水浩

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第８回鎌田泉博士論文賞

2002.3

平沢敬

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Research Projects

出芽酵母におけるグリセロール資化の新規メカニズム解明と有用物質発酵生産への応用

2023.4 - 2025.3

公益財団法人小林財団第１１回（令和４年度）研究助成

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Authorship：Principal investigator

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人工代謝経路を利用したO-アセチルホモセリン微生物発酵生産の高効率化

2022 - 2023

科学技術振興機構産学が連携した研究開発成果の展開研究成果展開事業研究成果最適展開支援プログラム(A-STEP) トライアウトトライアウト

平沢敬

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Authorship：Principal investigator

本研究では、細胞の環境適応・進化機構に基づいて、微生物に導入した人工代謝経路の代謝フラックス強化を実現させる。そして、フラックスが強化された人工代謝経路の反応を利用することで、アミノ酸の一種であるメチオニンの工業的生産における出発物質であるO-アセチルホモセリンの微生物による発酵生産を高効率化する。

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J-GLOBAL
進化工学によるメチルトランスフェラーゼ反応フラックスの強化と抗酸化能を持つエルゴチオネインの微生物発酵生産系への応用

2021.4 - 2022.3

公益財団法人小柳財団 2020年度研究助成

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Authorship：Principal investigator

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使用済タイヤ（廃ゴム）からの化学品製造技術の開発

Grant number：21578630 2021 - 2028.3

国立研究開発法人新エネルギー・産業技術総合開発機構グリーンイノベーション基金事業・ＣＯ２等を用いたプラスチック原料製造技術開発／研究開発項目2「廃プラ・廃ゴムからの化学品製造技術の開発」

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Authorship：Coinvestigator(s)

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実験室進化を基盤とするコリネ型細菌システイン耐性株の創製と含硫有用物質生産への応用

2018.4 - 2019.3

公益財団法人すかいらーくフードサイエンス研究所第31回学術助成

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Authorship：Principal investigator

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定常期における有用物質生産に向けた微生物の細胞増殖・代謝を制御する化合物の探索

2016.4 - 2019.3

日本学術振興会科研費挑戦的萌芽研究

平沢敬

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Authorship：Principal investigator Grant type：Competitive

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炭素・窒素・硫黄メタボリックフローの統合的改変育種によるエルゴチオネイン発酵生産

2015.4 - 2018.3

農林水産省農林水産業・食品産業科学技術研究推進事業委託事業

大津厳生

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Grant type：Competitive

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実験進化過程のマルチオミクス解析によるストレス耐性細胞工場の創製

2012.4 - 2016.3

日本学術振興会科研費基盤研究(A)

清水浩

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Grant type：Competitive

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汎用的高効率バイオプロセス細胞の創製

2011.3 - 2016.3

科学技術振興機構先端的低炭素化技術開発

小笠原直毅

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Grant type：Competitive

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Study on inhibitory effect of high light on the cell growth and adaptation mechanism of cyanobacteria

Grant number：23656526 2011 - 2012

Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research

SHIMIZU Hiroshi, FURUSAWA Chikara, HIRASAWA Takashi

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Grant amount：\3900000 （ Direct Cost: \3000000 、 Indirect Cost：\900000 ）

Effect of light irradiation strength on growth of cyanobacteria Synechocystis sp. PCC 6803 was investigated to establish a new strategy for creation of high light stress tolerant strain keeping high growth and production ability under high light condition. It was succeeded that the cell growth activity was quantitatively evaluated and DNA microarray analysis was performed under several light intensity conditions. It is expected that the results of analysis could provide a fundamental basis for design of high light tolerant strains of cyanobacteria for industrial purpose.

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Creation of stress tolerant strain based on single nucleotide mutational analysis of in whole genome

Grant number：21360401 2009 - 2011

Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

SHIMIZU Hiroshi, FURUSAWA Chikara, HIRASAWA Takashi, ONO Naoaki

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Grant amount：\17550000 （ Direct Cost: \13500000 、 Indirect Cost：\4050000 ）

We performed experimental evolution under(5%) ethanol stress condition in Escherichia coli and six ethanol stress tolerant evolved strains were independently obtained. Transcriptomic analysis of evolved strains was performed. As a result of principal component analysis(PCA), gene expression in biosynthesis pathways of some amino acids were extracted and these are commonly up-regulated in the tolerant strains, suggesting that activating these pathways were involved in the achievement of ethanol tolerance. In support of this hypothesis, the supplementation of these amino acids to the culture medium increased the specific growth rate under ethanol stress. Mutational analysis was also performed by high-density oligonucleotide microarray and it was suggested that mutation does not significantly contribute to ethanol stress tolerance because there few common mutations among evolved strains.

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Optimization of technologies for improving microbial metabolisms using antisense RNA expression system

Grant number：21780071 2009 - 2010

Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)

HIRASAWA Takashi

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Grant amount：\4550000 （ Direct Cost: \3500000 、 Indirect Cost：\1050000 ）

In this study, effectiveness of antisense RNA expression system was examined using antisense RNA expression system for odhA mRNA of a coryneform bacterium Corynebacterium glutamicum. Moreover, effective design of antisense RNA for improving metabolisms and optimization of antisense RNA expression system were tried by constructing the antisense RNAs with various length and those based on the secondary structure of target mRNA.

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Metabolic dynamics analysis in Escherichia coli toward understanding metabolic regulation and design of useful strains

Grant number：19780061 2007 - 2008

Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)

HIRASAWA Takashi

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Grant amount：\3690000 （ Direct Cost: \3300000 、 Indirect Cost：\390000 ）

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In silica Design of Metabolic Pathway of Yet for Bio-ProductionofEnvironmental-Conscious Chemical Products

Grant number：18360395 2006 - 2007

Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

SHIMIZU Hiroshi, FURUSAWA Chikara, HIRASAWA Takashi

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Grant amount：\17130000 （ Direct Cost: \15600000 、 Indirect Cost：\1530000 ）

The objective of this study is to establish a genome-scale model for prediction of change of metabolic pathways and design methodology for production of environmental-conscious chemicals in yeast. Seocharomyces cerevisiae was used as a model microorganism for this objective. A novel method to predict in silico effect of change of gene expression level on change of metabolic fluxes in the cells was developed.
Genome scale model was constructed by integration of genome information as a set of stoichiometric form of metabolic reactions. This model does not involve any kinetic information and this enables us to minimize the load of the model construction and parameter estimation in the model. Targeted chemicals for environmental-conscious materials are selected in the metabolic pathways of central carbon metabolism around glycolysis, TCA cycle, biosynthesis of amino acids. Modification of metabolic pathways based on the gene knock out was designed with the developed system.
An experimental validation and evaluation system for metabolic flux change was also developed. Precise metabolic flux evaluation system for central carbon metabolism of yeast was established.130-labeled chemical compound was consumed by cells experimentally and enrichment of labeled carbon was analyzed by gas chromatography mass spectrometry (GC-MS). For achieving the objective, a central carbon metabolism model was constructed by taking into amount of atom mapping.
The systems developed in this study were well developed and applied for production of succinic acid in yeast.

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Teaching Experience

Environment and Safety

2024.4 Institution：Institute of Science Tokyo / Tokyo Institute of Technology

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生物代謝科学

2016.4 Institution：東京科学大学 / 東京工業大学

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生命理工学基礎実験・演習

2016.4 Institution：東京科学大学 / 東京工業大学

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生物化学工学

2016.4 Institution：東京科学大学 / 東京工業大学

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微生物学

2016.4 Institution：東京科学大学 / 東京工業大学

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微生物工学

2014 - 2015 Institution：東京工業大学

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基礎生物学

2014 - 2015 Institution：東京工業大学

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生物化学

2013 - 2015 Institution：東京工業大学

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