Improvement of oxidized glutathione fermentation by thiol redox metabolism engineering in Saccharomyces cerevisiae

Verfasser / Beitragende:
[Kiyotaka Hara, Naoko Aoki, Jyumpei Kobayashi, Kentaro Kiriyama, Keiji Nishida, Michihiro Araki, Akihiko Kondo]
Ort, Verlag, Jahr:
2015
Enthalten in:
Applied Microbiology and Biotechnology, 99/22(2015-11-01), 9771-9778
Format:
Artikel (online)
ID: 605500908
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024 7 0 |a 10.1007/s00253-015-6847-z  |2 doi 
035 |a (NATIONALLICENCE)springer-10.1007/s00253-015-6847-z 
245 0 0 |a Improvement of oxidized glutathione fermentation by thiol redox metabolism engineering in Saccharomyces cerevisiae  |h [Elektronische Daten]  |c [Kiyotaka Hara, Naoko Aoki, Jyumpei Kobayashi, Kentaro Kiriyama, Keiji Nishida, Michihiro Araki, Akihiko Kondo] 
520 3 |a Glutathione is a valuable tripeptide widely used in the pharmaceutical, food, and cosmetic industries. In industrial fermentation, glutathione is currently produced primarily using the yeast Saccharomyces cerevisiae. Intracellular glutathione exists in two forms; the majority is present as reduced glutathione (GSH) and a small amount is present as oxidized glutathione (GSSG). However, GSSG is more stable than GSH and is a more attractive form for the storage of glutathione extracted from yeast cells after fermentation. In this study, intracellular GSSG content was improved by engineering thiol oxidization metabolism in yeast. An engineered strain producing high amounts of glutathione from over-expression of glutathione synthases and lacking glutathione reductase was used as a platform strain. Additional over-expression of thiol oxidase (1.8.3.2) genes ERV1 or ERO1 increased the GSSG content by 2.9-fold and 2.0-fold, respectively, compared with the platform strain, without decreasing cell growth. However, over-expression of thiol oxidase gene ERV2 showed almost no effect on the GSSG content. Interestingly, ERO1 over-expression did not decrease the GSH content, raising the total glutathione content of the cell, but ERV1 over-expression decreased the GSH content, balancing the increase in the GSSG content. Furthermore, the increase in the GSSG content due to ERO1 over-expression was enhanced by additional over-expression of the gene encoding Pdi1, whose reduced form activates Ero1 in the endoplasmic reticulum. These results indicate that engineering the thiol redox metabolism of S. cerevisiae improves GSSG and is critical to increasing the total productivity and stability of glutathione. 
540 |a Springer-Verlag Berlin Heidelberg, 2015 
690 7 |a Oxidized glutathione  |2 nationallicence 
690 7 |a Thiol oxidase  |2 nationallicence 
690 7 |a Yeast  |2 nationallicence 
690 7 |a Saccharomyces cerevisiae  |2 nationallicence 
690 7 |a Metabolic engineering  |2 nationallicence 
690 7 |a Cell factory  |2 nationallicence 
700 1 |a Hara  |D Kiyotaka  |u Organization of Advanced Science and Technology, Kobe University, 1-1 Rokkodai-cho, 657-8501, Kobe, Nada-ku, Japan  |4 aut 
700 1 |a Aoki  |D Naoko  |u Organization of Advanced Science and Technology, Kobe University, 1-1 Rokkodai-cho, 657-8501, Kobe, Nada-ku, Japan  |4 aut 
700 1 |a Kobayashi  |D Jyumpei  |u Organization of Advanced Science and Technology, Kobe University, 1-1 Rokkodai-cho, 657-8501, Kobe, Nada-ku, Japan  |4 aut 
700 1 |a Kiriyama  |D Kentaro  |u Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, 1-1 Rokkodaicho, 657-8501, Kobe, Nada-ku, Japan  |4 aut 
700 1 |a Nishida  |D Keiji  |u Organization of Advanced Science and Technology, Kobe University, 1-1 Rokkodai-cho, 657-8501, Kobe, Nada-ku, Japan  |4 aut 
700 1 |a Araki  |D Michihiro  |u Organization of Advanced Science and Technology, Kobe University, 1-1 Rokkodai-cho, 657-8501, Kobe, Nada-ku, Japan  |4 aut 
700 1 |a Kondo  |D Akihiko  |u Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, 1-1 Rokkodaicho, 657-8501, Kobe, Nada-ku, Japan  |4 aut 
773 0 |t Applied Microbiology and Biotechnology  |d Springer Berlin Heidelberg  |g 99/22(2015-11-01), 9771-9778  |x 0175-7598  |q 99:22<9771  |1 2015  |2 99  |o 253 
856 4 0 |u https://doi.org/10.1007/s00253-015-6847-z  |q text/html  |z Onlinezugriff via DOI 
898 |a BK010053  |b XK010053  |c XK010000 
900 7 |a Metadata rights reserved  |b Springer special CC-BY-NC licence  |2 nationallicence 
908 |D 1  |a research-article  |2 jats 
949 |B NATIONALLICENCE  |F NATIONALLICENCE  |b NL-springer 
950 |B NATIONALLICENCE  |P 856  |E 40  |u https://doi.org/10.1007/s00253-015-6847-z  |q text/html  |z Onlinezugriff via DOI 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Hara  |D Kiyotaka  |u Organization of Advanced Science and Technology, Kobe University, 1-1 Rokkodai-cho, 657-8501, Kobe, Nada-ku, Japan  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Aoki  |D Naoko  |u Organization of Advanced Science and Technology, Kobe University, 1-1 Rokkodai-cho, 657-8501, Kobe, Nada-ku, Japan  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Kobayashi  |D Jyumpei  |u Organization of Advanced Science and Technology, Kobe University, 1-1 Rokkodai-cho, 657-8501, Kobe, Nada-ku, Japan  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Kiriyama  |D Kentaro  |u Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, 1-1 Rokkodaicho, 657-8501, Kobe, Nada-ku, Japan  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Nishida  |D Keiji  |u Organization of Advanced Science and Technology, Kobe University, 1-1 Rokkodai-cho, 657-8501, Kobe, Nada-ku, Japan  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Araki  |D Michihiro  |u Organization of Advanced Science and Technology, Kobe University, 1-1 Rokkodai-cho, 657-8501, Kobe, Nada-ku, Japan  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Kondo  |D Akihiko  |u Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, 1-1 Rokkodaicho, 657-8501, Kobe, Nada-ku, Japan  |4 aut 
950 |B NATIONALLICENCE  |P 773  |E 0-  |t Applied Microbiology and Biotechnology  |d Springer Berlin Heidelberg  |g 99/22(2015-11-01), 9771-9778  |x 0175-7598  |q 99:22<9771  |1 2015  |2 99  |o 253