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

Melanie Nguyen; Maxime Le Mignon; Alisa Schnellbächer; Maria Wehsling; Julian Braun; Jens Baumgaertner; Martina Grabner; Aline Zimmer

doi:10.3389/fbioe.2023.1230422

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

Front Bioeng Biotechnol. 2023 Aug 23:11:1230422. doi: 10.3389/fbioe.2023.1230422. eCollection 2023.

Authors

Melanie Nguyen^{1

2}, Maxime Le Mignon¹, Alisa Schnellbächer¹, Maria Wehsling¹, Julian Braun¹, Jens Baumgaertner³, Martina Grabner¹, Aline Zimmer¹

Affiliations

¹ Upstream R&D, Merck Life Science KGaA, Darmstadt, Germany.
² Institute for Organic Chemistry and Biochemistry, Technische Universität Darmstadt, Darmstadt, Germany.
³ Biomolecule Analytics and Proteomics, Merck KGaA, Darmstadt, Germany.

Abstract

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.

Keywords: CHO; S-sulfocysteine; biological activity; omics; redox control.

Grants and funding

This study received funding from Merck Life Science KGaA. The funder was not involved in the study design, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.