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Mechanistic insights into the biological activity of S-Sulfocysteine in CHO cells using a multi-omics approach

S-Sulfocysteine (SSC), a bioavailable L-cysteine derivative (Cys), is known to be taken up and metabolized in Chinese hamster ovary (CHO) cells used to produce novel therapeutic biological entities. To gain a deeper mechanistic insight into the SSC biological activity and metabolization, a multi-omi...

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Autores principales: Nguyen, Melanie, Le Mignon, Maxime, Schnellbächer, Alisa, Wehsling, Maria, Braun, Julian, Baumgaertner, Jens, Grabner, Martina, Zimmer, Aline
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10482334/
https://www.ncbi.nlm.nih.gov/pubmed/37680342
http://dx.doi.org/10.3389/fbioe.2023.1230422
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author Nguyen, Melanie
Le Mignon, Maxime
Schnellbächer, Alisa
Wehsling, Maria
Braun, Julian
Baumgaertner, Jens
Grabner, Martina
Zimmer, Aline
author_facet Nguyen, Melanie
Le Mignon, Maxime
Schnellbächer, Alisa
Wehsling, Maria
Braun, Julian
Baumgaertner, Jens
Grabner, Martina
Zimmer, Aline
author_sort Nguyen, Melanie
collection PubMed
description S-Sulfocysteine (SSC), a bioavailable L-cysteine derivative (Cys), is known to be taken up and metabolized in Chinese hamster ovary (CHO) cells used to produce novel therapeutic biological entities. To gain a deeper mechanistic insight into the SSC biological activity and metabolization, a multi-omics study was performed on industrially relevant CHO-K1 GS cells throughout a fed-batch process, including metabolomic and proteomic profiling combined with multivariate data and pathway analyses. Multi-layered data and enzymatical assays revealed an intracellular SSC/glutathione mixed disulfide formation and glutaredoxin-mediated reduction, releasing Cys and sulfur species. Increased Cys availability was directed towards glutathione and taurine synthesis, while other Cys catabolic pathways were likewise affected, indicating that cells strive to maintain Cys homeostasis and cellular functions.
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spelling pubmed-104823342023-09-07 Mechanistic insights into the biological activity of S-Sulfocysteine in CHO cells using a multi-omics approach Nguyen, Melanie Le Mignon, Maxime Schnellbächer, Alisa Wehsling, Maria Braun, Julian Baumgaertner, Jens Grabner, Martina Zimmer, Aline Front Bioeng Biotechnol Bioengineering and Biotechnology S-Sulfocysteine (SSC), a bioavailable L-cysteine derivative (Cys), is known to be taken up and metabolized in Chinese hamster ovary (CHO) cells used to produce novel therapeutic biological entities. To gain a deeper mechanistic insight into the SSC biological activity and metabolization, a multi-omics study was performed on industrially relevant CHO-K1 GS cells throughout a fed-batch process, including metabolomic and proteomic profiling combined with multivariate data and pathway analyses. Multi-layered data and enzymatical assays revealed an intracellular SSC/glutathione mixed disulfide formation and glutaredoxin-mediated reduction, releasing Cys and sulfur species. Increased Cys availability was directed towards glutathione and taurine synthesis, while other Cys catabolic pathways were likewise affected, indicating that cells strive to maintain Cys homeostasis and cellular functions. Frontiers Media S.A. 2023-08-23 /pmc/articles/PMC10482334/ /pubmed/37680342 http://dx.doi.org/10.3389/fbioe.2023.1230422 Text en Copyright © 2023 Nguyen, Le Mignon, Schnellbächer, Wehsling, Braun, Baumgaertner, Grabner and Zimmer. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Bioengineering and Biotechnology
Nguyen, Melanie
Le Mignon, Maxime
Schnellbächer, Alisa
Wehsling, Maria
Braun, Julian
Baumgaertner, Jens
Grabner, Martina
Zimmer, Aline
Mechanistic insights into the biological activity of S-Sulfocysteine in CHO cells using a multi-omics approach
title Mechanistic insights into the biological activity of S-Sulfocysteine in CHO cells using a multi-omics approach
title_full Mechanistic insights into the biological activity of S-Sulfocysteine in CHO cells using a multi-omics approach
title_fullStr Mechanistic insights into the biological activity of S-Sulfocysteine in CHO cells using a multi-omics approach
title_full_unstemmed Mechanistic insights into the biological activity of S-Sulfocysteine in CHO cells using a multi-omics approach
title_short Mechanistic insights into the biological activity of S-Sulfocysteine in CHO cells using a multi-omics approach
title_sort mechanistic insights into the biological activity of s-sulfocysteine in cho cells using a multi-omics approach
topic Bioengineering and Biotechnology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10482334/
https://www.ncbi.nlm.nih.gov/pubmed/37680342
http://dx.doi.org/10.3389/fbioe.2023.1230422
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