Continuous improvements of cell culture media are required in order to ensure high yield and product quality. However, some components can be instable and lead to detrimental effects on bioprocess performances. l-cysteine is an essential amino acid commonly used in cell culture media. Despite its beneficial effect on recombinant protein production, in some cases, this component can be responsible for product microheterogeneity. In this context, alternative components have to be found in order to reduce product variants while maintaining high productivity. In this study, we have assessed the performance of different cysteine and cystine analogs : N-acetyl-cysteine, s-sulfocysteine, N,N′-diacetyl-l-cystine and the N,N′-diacetyl-l-cystine dimethylester (DACDM). Replacement of cysteine by cystine analogs, and especially DACDM, has shown positive impact on charge variants level and recombinant protein coloration level. Moreover, this molecule contributed to the increase of the intracellular glutathione pool, which suggests a close relationship with the oxidative stress regulation.

需要不断改进细胞培养基，以确保高产量和产品质量。但是，某些组件可能不稳定并导致对生物过程性能的不利影响。l -半胱氨酸是细胞培养基中常用的必需氨基酸。尽管它对重组蛋白生产有益，但在某些情况下，该成分可能导致产品微观异质性。在这种情况下，必须找到替代组件，以减少产品变体，同时保持高生产率。在本研究中，我们评估了不同半胱氨酸和胱氨酸类似物的性能：N-乙酰半胱氨酸、s-磺基半胱氨酸、N,N'-二乙酰-l-胱氨酸和 N,N'-二乙酰-l-胱氨酸二甲酯 (DACDM)。用胱氨酸类似物替代半胱氨酸，尤其是 DACDM，已显示出对电荷变异水平和重组蛋白着色水平的积极影响。此外，该分子有助于细胞内谷胱甘肽库的增加，这表明与氧化应激调节密切相关。