UCB Nordic A/S, Upstream Process Sciences, Copenhagen, Denmark; Technical University of Denmark, Department of Biotechnology and Biomedicine, Kgs. Lyngby, Denmark.
UCB Pharma S.A., Upstream Process Sciences, Braine l'Alleud, Belgium.
J Biotechnol. 2021 Feb 10;327:1-8. doi: 10.1016/j.jbiotec.2020.12.011. Epub 2020 Dec 26.
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.
为了确保高产量和产品质量，需要不断改进细胞培养基。然而，一些成分可能不稳定，并对生物工艺性能产生不利影响。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有益的影响，但在某些情况下，这种成分可能会导致产品的微观不均一性。在这种情况下，必须找到替代成分，以在保持高生产力的同时减少产品变体。在这项研究中，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、半胱氨酸磺酸、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，特别是 DACDM，对电荷变异体水平和重组蛋白着色水平有积极影响。此外，这种分子有助于增加细胞内谷胱甘肽池，这表明它与氧化应激调节密切相关。
