Graduate School of Information Science and Technology,
Osaka University
Shimizu Lab.
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Graduate School of Information Science and Technology,
Osaka University
Shimizu Lab.

Member

Yoshihiro Toya

研究テーマ

光による代謝フラックスの制御技術の開発

ロドプシンを利用した光駆動ATP再生の物質生産への応用

代謝状態の可視化とバイオプロセス制御への応用

共培養を利用した代謝工学技術の開発

代謝経路の律速段階の予測と解消

シミュレーションに基づく代謝経路の合理的設計

13C代謝フラックス解析による細胞内代謝状態の評価

経歴

2010年 慶應義塾大学 博士（学術）
2010年 慶應義塾大学 大学院 政策メディア研究科 特任助教
2011年 大阪大学 大学院情報科学研究科 特任助教
2015年 大阪大学 大学院情報科学研究科 助教
2018年 大阪大学 大学院情報科学研究科 准教授


受賞

2022年　日本生物工学会　第45回生物工学奨励賞（照井賞）「光を利用したバイオプロセスの開発に関する研究」

2019年　大阪大学　大阪大学賞（若手教員部門）「微生物による有用物質生産の高効率化の ための代謝フラックス制御の研究」


[研究者総覧]

[Rsearchmap]


ミニ講義　in silico and in vivo approaches for microbial metabolic engineering


原著論文

  1. Ueno K, Sawada S, Ishibashi M, Kanda Y, Shimizu H, Toya Y*.
    Identification of a novel NADPH generation reaction in the pentose phosphate pathway in Escherichia coli using mBFP.
    J Bacteriol. in press
  2. Hirose Y, Zielinski DC, Poudel S, Rychel K, Baker JL, Toya Y, Yamaguchi M, Heinken A, Thiele I, Kawabata S, Palsson BO, Nizet V.
    A genome-scale metabolic model of a globally disseminated hyperinvasive M1 strain of Streptococcus pyogenes.
    mSystems. 2024; 9(9): e0073624
  3. Effendi SSW, Toya Y, Shimizu H, Xue C, Ng IS.
    Utilizing Ribose 1,5-Bisphosphate Isomerase and RuBisCO-Equipped Escherichia coli Nissle for Low-Carbon Footprint GABA Production.
    ACS Sustain Chem Eng. 2024; 12(30): 11093–11098.
  4. Mori H, Matsui M, Bamba T, Hori Y, Kitamura S, Toya Y, Hidese R, Yasueda H, Hasunuma T, Shimizu H, Taoka N, Kobayashi S.
    Engineering Escherichia coli for efficient glutathione production.
    Metab Eng. 2024; 84: 180-190.
  5. Matsuyama C, Seike T, Okahashi N, Niide T, Hara KY, Hirono-Hara Y, Ishii J, Shimizu H, Toya Y, Matsuda F.
    Metabolome analysis of metabolic burden in Escherichia coli caused by overexpression of green fluorescent protein and delta-rhodopsin.
    J Biosci Bioeng. 2024; 137(3): 187-194.
  6. Akagi H, Shimizu H, Toya Y*.
    Multicolor optogenetics for regulating flux ratio of three glycolytic pathways using EL222 and CcaSR in Escherichia coli.
    Biotechnol Bioeng. 2024; 121(3): 1016-1025.
  7. Wada K, Uebayashi K, Toya Y, Putri SP, Matsuda F, Fukusaki E, Liao JC, Shimizu H.
    Effects of n-butanol production on metabolism and the photosystem in Synechococcus elongatus PCC 7942 based on metabolic flux and target proteome analyses.
    J Gen Appl Microbiol. 2024; 69(4):185-195.
  8. Miyoshi K, Kawai R, Niide T, Toya Y, Shimizu H.
    Functional evaluation of non-oxidative glycolysis in Escherichia coli in the stationary phase under microaerobic conditions.
    J Biosci Bioeng. 2023; 135(4):291-297.
  9. Imada T, Yamamoto C, Toyoshima M, Toya Y, Shimizu H.
    Effect of light fluctuations on photosynthesis and metabolic flux in Synechocystis sp. PCC 6803.
    Biotechnol Prog. 2023; 39(3):e3326.
  10. Sano M, Tanaka R, Kamata K, Hirono-Hara Y, Ishii J, Matsuda F, Hara KY, Shimizu H, Toya Y*.
    Conversion of mevalonate to isoprenol using light energy in Escherichia coli without consuming sugars for ATP supply.
    ACS Synth Biol. 2022; 11(12), 3966–3972.
  11. Sugiki S, Niide T, Toya Y, Shimizu H.
    Logistic regression-guided identification of cofactor specificity-contributing residues in enzyme with sequence datasets partitioned by catalytic properties.
    ACS Synth Biol. 2022; 11(12), 3973–3985.
  12. Otsuka K, Seike T, Toya Y, Ishii J, Hirono-Hara Y, Hara KY, Matsuda F.
    Evolutionary approach for improved proton pumping activity of heterologous rhodopsin expressed in Escherichia coli.
    J Biosci Bioeng. 2022;134(6):484-490.
  13. Kawai R, Toya Y, Shimizu H.
    Metabolic pathway design for growth-associated phenylalanine production using synthetically designed mutualism.
    Bioprocess Biosyst Eng. 2022; 45(9): 1539-1546.
  14. Toya Y*, Shimizu H.
    Metabolic pathway engineering for the non-growth-associated succinate production in Escherichia coli based on flux solution space.
    J Biosci Bioeng. 2022; 134(1): 29-33.
  15. Yamamoto J, Chumsakul O, Toya Y, Morimoto T, Liu S, Masuda K, Kageyama Y, Hirasawa T, Matsuda F, Ogasawara N, Shimizu H, Yoshida KI, Oshima T, Ishikawa S.
    Constitutive expression of the global regulator AbrB restores the growth defect of a genome-reduced Bacillus subtilis strain and improves its metabolite production.
    DNA Res. 2022; 29(3):dsac015.
  16. Toya Y, Hirono-Hara Y, Hirayama H, Kamata K, Tanaka R, Sano M, Kitamura S, Otsuka K, Abe-Yoshizumi R, Tsunoda SP, Kikukawa H, Kandori H, Shimizu H, Matsuda F, Ishii J, Hara KY.
    Optogenetic reprogramming of carbon metabolism using light-powering microbial proton pump systems.
    Metab Eng. 2022; 72: 227-236.【プレスリリース】
  17. Kawai R, Toya Y, Miyoshi K, Murakami M, Niide T, Horinouchi T, Maeda T, Shibai A, Furusawa C, Shimizu H.
    Acceleration of target production in co-culture by enhancing intermediate consumption through adaptive laboratory evolution.
    Biotechnol Bioeng. 2022; 119(3): 936-945.
  18. Kusuda M, Shimizu H, Toya Y*.
    Reactor control system in bacterial co-culture based on fluorescent proteins using an Arduino-based home-made device.
    Biotechnol J. 2021; 16: 2100169.
  19. Tokuyama K, Shimodaira Y, Kodama Y, Matsui R, Kusunose Y, Fukushima S, Nakai H, Tsuji Y, Toya Y, Matsuda F, Shimizu H.
    Soft-sensor development for monitoring the lysine fermentation process.
    J Biosci Bioeng. 2021; 132(2): 183-189.
  20. Toyoshima M, Sakata M, Ueno Y, Toya Y, Matsuda F, Akimoto S, Shimizu H.
    Proteome analysis of response to different spectral light irradiation in Synechocystis sp. PCC 6803.
    J Proteomics. 2021; 246: 104306.
  21. Yoshikawa K#, Ogawa K#, Toya Y#, Akimoto S, Matsuda F, Shimizu H.
    Mutations in hik26 and slr1916 lead to high-light stress tolerance in Synechocystis sp. PCC6803.
    Commun Biol. 2021; 4(1): 343.【プレスリリース】
  22. Kitamura S, Shimizu H, Toya Y*.
    Identification of a rate-limiting step in a metabolic pathway using the kinetic model and in vitro experiment.
    J Biosci Bioeng. 2021; 131(3): 271-276.
  23. Yamamoto C, Toyoshima M, Kitamura S, Ueno Y, Akimoto S, Toya Y, Shimizu H.
    Estimation of linear and cyclic electron flows in photosynthesis based on 13C-metabolic flux analysis.
    J Biosci Bioeng. 2021; 131(3): 277-282.
  24. Toyoshima M, Yamamoto C, Ueno Y, Toya Y, Akimoto S, Shimizu H.
    Role of type I NADH dehydrogenase in Synechocystis sp. PCC 6803 under phycobilisome excited red light.
    Plant Sci. 2021; 304: 110798.
  25. Tokuyama K, Shimodaira Y, Terawaki T, Kusunose Y, Nakai H, Tsuji Y, Toya Y, Matsuda F, Shimizu H.
    Data science-based modeling of the lysine fermentation process.
    J Biosci Bioeng. 2020; 130(4): 409-415.
  26. Nochino N, Toya Y, Shimizu H.
    Transcription factor ArcA is a flux sensor for the oxygen consumption rate in Escherichia coli.
    Biotechonol J. 2020; 15(6): e1900353.
  27. Toyoshima M, Toya Y, Shimizu H.
    Flux balance analysis of cyanobacteria reveals selective use of photosynthetic electron transport components under different spectral light conditions.
    Photosynth Res. 2020; 143(1): 31–43.
  28. Senoo S, Tandar ST, Kitamura S, Toya Y*, Shimizu H.
    Light-inducible flux control of triosephosphate isomerase on glycolysis in Escherichia coli.
    Biotechnol Bioeng. 2019; 116(12): 3292-3300.
  29. Hanatani Y, Imura M, Taniguchi H, Okano K, Toya Y, Iwakiri R, Honda K.
    In vitro production of cysteine from glucose.
    Appl Microbiol Biotechnol. 2019; 103(19): 8009-8019. 
  30. Tandar ST, Senoo S, Toya Y, Shimizu H.
    Optogenetic switch for controlling the central metabolic flux of Escherichia coli.
    Metab Eng. 2019; 55: 68-75.【プレスリリース】
  31. Tokuyama K, Toya Y, Shimizu H.
    Prediction of rate-limiting reactions for growth-associated production using a constraint-based approach.
    Biotechnol J. 2019; 14: e1800431.
  32. Adachi S, Tanaka Y, Miyagi A, Kashima M, Tezuka A, Toya Y, Kobayashi S, Ohkubo S, Shimizu H, Kawai-Yamada M, Sage RF, Nagano AJ, Yamori W.
    High-yielding rice Takanari has superior photosynthetic response under fluctuating light to a commercial rice Koshihikari.
    J Exp Bot. 2019; 70(19): 5287-5297.
  33. Kitamura S, Toya Y, Shimizu H.
    13C-metabolic flux analysis reveals effect of phenol on central carbon metabolism in Escherichia coli.
    Front Microbiol. 2019; 10: 1010.
  34. Kamiura R, Toya Y*, Matsuda F, Shimizu H.
    Theophylline-inducible riboswitch accurately regulates protein expression at low level in Escherichia coli.
    Biotechnol Lett. 2019; 41: 743-751.
  35. Kamata K, Toya Y, Shimizu H.
    Effect of precise control of flux ratio between the glycolytic pathways on mevalonate production in Escherichia coli.
    Biotechnol Bioeng. 2019; 116(5): 1080-1088.
  36. Tokuyama K, Toya Y, Matsuda F, Cress BF, Koffas MAG, Shimizu H.
    Magnesium starvation improves production of malonyl-CoA-derived metabolites in Escherichia coli.
    Metab Eng. 2019; 52: 215-223.
  37. Ogawa K, Yoshikawa K, Matsuda F, Toya Y, Shimizu H.
    Transcriptome analysis of the cyanobacterium Synechocystis sp. PCC 6803 and mechanisms of photoinhibition tolerance under extreme high light conditions.
    J Biosci Bioeng. 2018; 126(5): 596-602.
  38. Maruyama Y, Toya Y, Kurokawa H, Fukano Y, Sato A, Umemura H, Yamada K, Iwasaki H, Tobori N, Shimizu H.
    Characterization of oil-producing yeast Lipomyces starkeyi on glycerol carbon source based on metabolomics and 13C-labeling.
    Appl Microbiol Biotechnol. 2018; 102(20): 8909-8920.
  39. Nagai H, Masuda A, Toya Y, Matsuda F, Shimizu H.
    Metabolic engineering of mevalonate-producing Escherichia coli strains based on thermodynamic analysis.
    Metab Eng. 2018; 47: 1-9.
  40. Tokuyama K, Toya Y, Horinouchi T, Furusawa C, Matsuda F, Shimizu H.
    Application of adaptive laboratory evolution to overcome a flux limitation in an Escherichia coli production strain.
    Biotechnol Bioeng. 2018; 115(6): 1542-1551.
  41. Ueda K, Nakajima T, Yoshikawa K, Toya Y, Matsuda F, Shimizu H.
    Metabolic flux of the oxidative pentose phosphate pathway under low light conditions in Synechocystis sp. PCC 6803.
    J Biosci Bioeng. 2018; 126(1): 38-43.
  42. Toya Y, Ohashi S, Shimizu H.
    Optimal 13C-labeling of glycerol carbon source for precise flux estimation in Escherichia coli.
    J Biosci Bioeng. 2018; 125(3): 301-305.
  43. Matsusako T, Toya Y, Yoshikawa K, Shimizu H.
    Identification of alcohol stress tolerance genes of Synechocystis sp. PCC 6803 using adaptive laboratory evolution.
    Biotechnol Biofuels. 2017; 10: 307.
  44. Masuda A, Toya Y, Shimizu H.
    Metabolic impact of nutrient starvation in mevalonate-producing Escherichia coli.
    Bioresour Technol. 2017; 245(Pt B): 1634-1640.
  45. Nakajima T, Yoshikawa K, Toya Y, Matsuda F, Shimizu H.
    Metabolic flux analysis of the Synechocystis sp. PCC 6803 ΔnrtABCD mutant reveals a mechanism for metabolic adaptation to nitrogen-limited conditions.
    Plant Cell Physiol. 2017; 58(3): 537-545.
  46. Yoshikawa K, Toya Y, Shimizu H.
    Metabolic engineering of Synechocystis sp. PCC 6803 for enhanced ethanol production based on flux balance analysis.
    Bioprocess Biosyst Eng. 2017; 40(5): 791-796.
  47. Wada K, Toya Y, Banno S, Yoshikawa K, Matsuda F, Shimizu H.
    13C-metabolic flux analysis for mevalonate-producing strain of Escherichia coli.
    J Biosci Bioeng. 2017; 123(2): 177-182.
  48. Namakoshi K, Nakajima T, Yoshikawa K, Toya Y, Shimizu H.
    Combinatorial deletions of glgC and phaCE enhance ethanol production in Synechocystis sp. PCC 6803.
    J Biotechnol. 2016; 239: 13-19.
  49. Maeda K, Okahashi N, Toya Y, Matsuda F, Shimizu H.
    Investigation of useful carbon tracers for 13C-metabolic flux analysis of Escherichia coli by considering five experimentally determined flux distributions.
    Metab Eng Commun. 2016; 3: 187–195.
  50. Yoshikawa K, Aikawa S, Kojima Y, Toya Y, Furusawa C, Kondo A, Shimizu H.
    Construction of a genome-scale metabolic model of Arthrospira platensis NIES-39 and metabolic design for cyanobacterial bioproduction.
    PLoS One 2015; 10(12): e0144430.
  51. Mannan AA, Toya Y, Shimizu K, McFadden J, Kierzek AM, Rocco A.
    Integrating kinetic model of E. coli with genome scale metabolic fluxes overcomes its open system problem and reveals bistability in central metabolism.
    PLoS One 2015; 10(10): e0139507.
  52. Toya Y, Hirasawa T, Ishikawa S, Chumsakul O, Morimoto T, Liu S, Masuda K, Kageyama Y, Ozaki K, Ogasawara N, Shimizu H.
    Enhanced dipicolinic acid production during the stationary phase in Bacillus subtilis by blocking acetoin synthesis.
    Biosci Biotechnol Biochem. 2015; 79(12): 2073-2080.
  53. Toya Y, Shiraki T, Shimizu H.
    SSDesign: Computational metabolic pathway design based on flux variability using elementary flux modes.
    Biotechnol Bioeng. 2015; 112(4): 759-768.
  54. Toya Y, Hirasawa T, Morimoto T, Masuda K, Kageyama Y, Ozaki K, Ogasawara N, Shimizu H.
    13C-metabolic flux analysis in heterologous cellulase production by Bacillus subtilis genome-reduced strain.
    J Biotechnol. 2014; 179: 42-49.
  55. Ito T, Sugimoto M, Toya Y, Ano Y, Kurano N, Soga T, Tomita M.
    Time-resolved metabolomics of a novel trebouxiophycean alga using 13CO2 feeding.
    J Biosci Bioeng. 2013; 116(3): 408-415.
  56. Toya Y, Nakahigashi K, Tomita M, Shimizu K.
    Metabolic regulation analysis of wild-type and arcA mutant Escherichia coli under nitrate conditions using different levels of omics data.
    Mol Biosyst. 2012; 8(10): 2593-2604.
  57. Yamamotoya T, Dose H, Tian Z, Fauré A, Toya Y, Honma M, Igarashi K, Nakahigashi K, Soga T, Mori H, Matsuno H.
    Glycogen is the primary source of glucose during the lag phase of E. coli proliferation.
    Biochim Biophys Acta. 2012; 1824(12): 1442-1448.
  58. Toya Y, Ishii N, Nakahigashi K, Hirasawa T, Soga T, Tomita M, Shimizu K.
    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.
    Biotechnol Prog. 2010; 26(4): 975-992.
  59. Nakahigashi K, Toya Y, Ishii N, Soga T, Hasegawa M, Watanabe H, Takai Y, Honma M, Mori H, Tomita M.
    Systematic phenome analysis of Escherichia coli multiple-knockout mutants reveals hidden reactions in central carbon metabolism.
    Mol Syst Biol. 2009; 5: 306.
  60. Toya Y, Ishii N, Hirasawa T, Naba M, Hirai K, Sugawara K, Igarashi S, Shimizu K, Tomita M, Soga T.
    Direct measurement of isotopomer of intracellular metabolites using capillary electrophoresis time-of-flight mass spectrometry for efficient metabolic flux analysis.
    J Chromatogr A 2007;1159(1-2):134-141.
  61. Ishii N, Nakahigashi K, Baba T, Robert M, Soga T, Kanai A, Hirasawa T, Naba M, Hirai K, Hoque A, Ho PY, Kakazu Y, Sugawara K, Igarashi S, Harada S, Masuda T, Sugiyama N, Togashi T, Hasegawa M, Takai Y, Yugi K, Arakawa K, Iwata N, Toya Y, Nakayama Y, Nishioka T, Shimizu K, Mori H, Tomita M.
    Multiple high-throughput analyses monitor the response of E. coli to perturbations.
    Science. 2007; 316(5824): 593-597.


総説

  1. Toya Y, Shimizu H.
    Coupling and uncoupling growth and product formation for producing chemicals.
    Curr Opin Biotechnol. 2024; 87: 103133.
  2. Shimizu H, Toya Y.
    Recent advances in metabolic engineering –integration of in silico design and experimental analysis of metabolic pathways.
    J Biosci Bioeng. 2021; 132(5):429-436.
  3. Toya Y, Shimizu H.
    Flux controlling technology for central carbon metabolism for efficient microbial bio-production.
    Curr Opin Biotechnol. 2020; 64:169-174.
  4. Matsuda F, Toya Y, Shimizu H.
    Learning from quantitative data to understand central carbon metabolism.
    Biotechnol Adv. 2017; 35(8):971-980.
  5. Toya Y, Shimizu H.
    Flux analysis and metabolomics for systematic metabolic engineering of microorganisms.
    Biotechnol Adv. 2013; 31(6):818-826.
  6. Toya Y, Kono N, Arakawa K, Tomita M.
    Metabolic flux analysis and visualization.
    J Proteome Res. 2011; 10(8):3313-3323.


解説

  1. 戸谷吉博, 代謝フラックス解空間に基づく大腸菌における増殖非連動型コハク酸生産のための代謝経路改変,  生物工学会誌 2024; 102(2):64-60.
  2. 戸谷吉博, 光を利用したバイオプロセスの開発に関する研究, 生物工学会誌 2023; 101(2):54-60.
  3. 清水浩, 戸谷吉博. 多様な光に適応する藍藻のシステムバイオロジー, 生物物理 2022; 62(2): 104-109.
  4. 戸谷吉博, 清水浩. 代謝シミュレーションを利用した有用物質生産微生物の開発, 化学工学会 バイオ部会ニュースレター 2021; 53: 14-18.
  5. 戸谷吉博, フラックス解析のいろいろ, 生物工学会誌 2021; 99(1):36.
  6. 戸谷吉博. シアノバクテリア由来の光応答スイッチの大腸菌代謝工学への利用, 生物工学会誌 2020; 98(11): 608-610.
  7. 戸谷吉博, 清水浩. 光照射により代謝フラックスをコントロールする技術の開発. バイオサイエンスとインダストリー 2020; 78(1): 30-31.
  8. 戸谷吉博, 松田史生. 代謝工学におけるバイオインフォマティクスの利用. 生物工学会誌 2019; 97(5): 261-264. 
  9. 戸谷吉博. 計算機シミュレーションを利用した代謝デザイン技術－有用物質生産の効率化を目的とした代謝経路の改変. 化学と生物 2017; 55(2): 83-85.
  10. 清水浩, 松田史生, 戸谷吉博. 代謝デザインと13C同位体標識を用いた代謝フラックス解析の物質生産への応用. 化学と生物 2015; 53(7): 455-461.
  11. 清水浩, 古澤力, 平沢敬, 吉川勝徳, 小野直亮, 戸谷吉博, 白井智量. 代謝工学の創成と発展－代謝解析とオミクス研究との融合. 生物工学会誌 2012; 90: 619-620.
  12. 戸谷吉博, 石井伸佳, 冨田勝. 微生物代謝のシステムバイオロジー ―オミックス解析からシミュレーションへ―. バイオインダストリー 2008; 25: 44-51.


著書

  1. 戸谷吉博, 清水浩. 第1章 4節 物質生産のための微生物代謝のin silicoデザイン. 微生物を用いた有用物質生産技術の開発, 技術情報協会, 分担執筆ページ 19-26 (2024). ISBN: 978-4-7813-1740-3
  2. 戸谷吉博, 松田史生, 石井純, 原清敬. 第1章 4 光をエネルギー源として利用する有用物質生産大腸菌の開発. 蓮沼誠久(監), シーエムシー出版, 分担執筆ページ 24-29 (2023). ISBN: 978-4-86798-023-1


その他

  1.  戸谷吉博, バイオ系のキャリアデザイン（就職支援OG・OBインタビュー編）Interview 1, 生物工学会誌 2022; 100(9):516-517.