Department of Chemical and Biochemical Engineering, Rice University, Houston, Texas, USA.
Systems, Synthetic, and Physical Biology, Rice University, Houston, Texas, USA.
Biotechnol Bioeng. 2023 Sep;120(9):2441-2459. doi: 10.1002/bit.28365. Epub 2023 Mar 11.
The production of high-quality recombinant proteins is critical to maintaining a continuous supply of biopharmaceuticals, such as therapeutic antibodies. Engineering mammalian cell factories presents a number of limitations typically associated with the proteotoxic stress induced upon aberrant accumulation of off-pathway protein folding intermediates, which eventually culminate in the induction of apoptosis. In this review, we will discuss advances in cell engineering and their applications at different hierarchical levels of control of the expression of recombinant proteins, from transcription and translational to posttranslational modifications and subcellular trafficking. We also highlight challenges and unique opportunities to apply modern synthetic biology tools to the design of programmable cell factories for improved biomanufacturing of therapeutic proteins.
生产高质量的重组蛋白对于维持生物制药（如治疗性抗体）的持续供应至关重要。工程化哺乳动物细胞工厂存在许多限制，这些限制通常与异常积累偏离途径的蛋白质折叠中间体引起的蛋白毒性应激有关，最终导致细胞凋亡。在这篇综述中，我们将讨论细胞工程的进展及其在不同层次的控制表达重组蛋白的应用，从转录和翻译到翻译后修饰和亚细胞运输。我们还强调了应用现代合成生物学工具设计可编程细胞工厂以改善治疗性蛋白的生物制造的挑战和独特机遇。
