Table1_Mechanistic insights into the biological activity of S-Sulfocysteine in CHO cells using a multi-omics approach.xlsx

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.

S-磺酰半胱氨酸（S-Sulfocysteine, SSC）是一种具备生物可利用性的L-半胱氨酸（L-cysteine, Cys）衍生物，已知可被用于生产新型治疗性生物制剂的中国仓鼠卵巢（Chinese hamster ovary, CHO）细胞摄取并代谢。为深入解析SSC的生物学活性与代谢机制，本研究针对工业生产相关的CHO-K1 GS细胞开展了补料分批培养过程中的多组学研究，涵盖代谢组学与蛋白质组学表征，并结合多变量数据分析与通路分析。多层组学数据与酶学实验证实，细胞内可形成SSC与谷胱甘肽的混合二硫键，并经谷氧还蛋白介导还原，释放半胱氨酸与含硫物质。半胱氨酸可用性的提升可导向谷胱甘肽与牛磺酸的合成，同时其他半胱氨酸分解代谢通路亦受到影响，这表明细胞会主动维持半胱氨酸稳态与细胞功能。