Institute of Biochemical Engineering, University of Stuttgart, Allmandring, Stuttgart, Germany.
Xell AG, Bielefeld, Germany.
Biotechnol Bioeng. 2020 Nov;117(11):3239-3247. doi: 10.1002/bit.27484. Epub 2020 Jul 22.
The improvement of cell specific productivities for the formation of therapeutic proteins is an important step towards intensified production processes. Among others, the induction of the desired production phenotype via proper media additives is a feasible solution provided that said compounds adequately trigger metabolic and regulatory programs inside the cells. In this study, S-(5'-adenosyl)- l-methionine (SAM) and 5'-deoxy-5'-(methylthio)adenosine (MTA) were found to stimulate cell specific productivities up to approx. 50% while keeping viable cell densities transiently high and partially arresting the cell cycle in an anti-IL-8-producing CHO-DP12 cell line. Noteworthy, MTA turned out to be the chemical degradation product of the methyl group donor SAM and is consumed by the cells.
提高治疗性蛋白形成的细胞特异性产率是强化生产工艺的重要步骤。除其他方法外，通过适当的培养基添加剂诱导所需的生产表型是一种可行的解决方案，前提是这些化合物能够充分触发细胞内的代谢和调节程序。在这项研究中，S-(5'-腺嘌呤核苷)- l-甲硫氨酸（SAM）和 5'-脱氧-5'-(甲基硫代)腺苷（MTA）被发现可将细胞特异性产率提高约 50%，同时使活细胞密度短暂升高，并在抗 IL-8 产生的 CHO-DP12 细胞系中部分阻断细胞周期。值得注意的是，MTA 是甲基供体 SAM 的化学降解产物，被细胞消耗。
