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https://hdl.handle.net/20.500.14094/90006449
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2024-04-25
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90006449 (fulltext)
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90006449
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open access
出版タイプ
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タイトル
Repression of mitochondrial metabolism for cytosolic pyruvate-derived chemical production in Saccharomyces cerevisiae
著者
Morita, Keisuke ; Matsuda, Fumio ; Okamoto, Koji ; Ishii, Jun ; Kondo, Akihiko ; Shimizu, Hiroshi
著者名
Morita, Keisuke
著者名
Matsuda, Fumio
著者名
Okamoto, Koji
著者ID
A1290
研究者ID
1000040512546
KUID
https://kuid-rm-web.ofc.kobe-u.ac.jp/search/detail?systemId=c06bf6c66d97f49e520e17560c007669
著者名
Ishii, Jun
石井, 純
イシイ, ジュン
所属機関名
先端バイオ工学研究センター
著者ID
A1715
研究者ID
1000040205547
KUID
https://kuid-rm-web.ofc.kobe-u.ac.jp/search/detail?systemId=a324eb4a1b052e53520e17560c007669
著者名
Kondo, Akihiko
近藤, 昭彦
コンドウ, アキヒコ
所属機関名
科学技術イノベーション研究科
著者名
Shimizu, Hiroshi
収録物名
Microbial Cell Factories
巻(号)
18(1)
ページ
177-177
出版者
BMC
刊行日
2019-10-15
公開日
2019-10-31
抄録
Background Saccharomyces cerevisiae is a suitable host for the industrial production of pyruvate-derived chemicals such as ethanol and 2,3-butanediol (23BD). For the improvement of the productivity of these chemicals, it is essential to suppress the unnecessary pyruvate consumption in S. cerevisiae to redirect the metabolic flux toward the target chemical production. In this study, mitochondrial pyruvate transporter gene (MPC1) or the essential gene for mitophagy (ATG32) was knocked-out to repress the mitochondrial metabolism and improve the production of pyruvate-derived chemical in S. cerevisiae. Results The growth rates of both aforementioned strains were 1.6-fold higher than that of the control strain. 13C-metabolic flux analysis revealed that both strains presented similar flux distributions and successfully decreased the tricarboxylic acid cycle fluxes by 50% compared to the control strain. Nevertheless, the intracellular metabolite pool sizes were completely different, suggesting distinct metabolic effects of gene knockouts in both strains. This difference was also observed in the test-tube culture for 23BD production. Knockout of ATG32 revealed a 23.6-fold increase in 23BD titer (557.0 ± 20.6 mg/L) compared to the control strain (23.5 ± 12.8 mg/L), whereas the knockout of MPC1 revealed only 14.3-fold increase (336.4 ± 113.5 mg/L). Further investigation using the anaerobic high-density fermentation test revealed that the MPC1 knockout was more effective for ethanol production than the 23BD production. Conclusion These results suggest that the engineering of the mitochondrial transporters and membrane dynamics were effective in controlling the mitochondrial metabolism to improve the productivities of chemicals in yeast cytosol.
キーワード
Saccharomyces cerevisiae
Mitophagy
Metabolome
Mitochondrial pyruvate carrier
13C-metabolic flux analysis
2,3-Butanediol
カテゴリ
科学技術イノベーション研究科
先端バイオ工学研究センター
学術雑誌論文
権利
© The Author(s) 2019.
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
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資源タイプ
journal article
言語
English (英語)
eISSN
1475-2859
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NCID
AA12039472
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関連情報
DOI
https://doi.org/10.1186/s12934-019-1226-6
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