Unit of Biochemistry and Molecular Biotechnology, Department of Biology, Ecology and Earth Sciences (DiBEST), University of Calabria, Via P. Bucci 4c, Arcavacata di Rende, 87036 Cosenza, Italy.
Institute of Biomembranes, Bioenergetics and Molecular Biotechnology (IBIOM), National Research Council (CNR), Via Amendola 165/A, 70126 Bari, Italy.
Int J Mol Sci. 2022 Mar 30;23(7):3823. doi: 10.3390/ijms23073823.
Ten percent of human genes encode for membrane transport systems, which are key components in maintaining cell homeostasis. They are involved in the transport of nutrients, catabolites, vitamins, and ions, allowing the absorption and distribution of these compounds to the various body regions. In addition, roughly 60% of FDA-approved drugs interact with membrane proteins, among which are transporters, often responsible for pharmacokinetics and side effects. Defects of membrane transport systems can cause diseases; however, knowledge of the structure/function relationships of transporters is still limited. Among the expression of hosts that produce human membrane transport systems, is one of the most favorable for its low cultivation costs, fast growth, handiness, and extensive knowledge of its genetics and molecular mechanisms. However, the expression in of human membrane proteins is often toxic due to the hydrophobicity of these proteins and the diversity in structure with respect to their bacterial counterparts. Moreover, differences in codon usage between humans and bacteria hamper translation. This review summarizes the many strategies exploited to achieve the expression of human transport systems in bacteria, providing a guide to help people who want to deal with this topic.
人类基因的 10%编码膜转运系统，它们是维持细胞内环境稳定的关键组成部分。这些系统参与营养物质、分解产物、维生素和离子的运输，使这些化合物能够被吸收和分布到身体的各个部位。此外，大约 60%的 FDA 批准的药物与膜蛋白相互作用，其中包括转运蛋白，它们通常负责药物代谢动力学和副作用。膜转运系统的缺陷会导致疾病；然而，转运蛋白的结构/功能关系的知识仍然有限。在产生人类膜转运系统的宿主表达中， 是最有利的一种，因为它的培养成本低、生长速度快、操作方便，并且对其遗传学和分子机制有广泛的了解。然而，由于这些蛋白质的疏水性以及与细菌对应物结构的多样性，它们在 中的表达往往是有毒的。此外，人类和细菌之间的密码子使用差异阻碍了翻译。这篇综述总结了许多用于在细菌中表达人类转运系统的策略，为希望处理这个课题的人提供了指导。
