Advanced stoichiometric analysis of metabolic networks of mammalian systems.
Advanced stoichiometric analysis of metabolic networks of mammalian systems.
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DOI：
10.1615/critrevbiomedeng.v39.i6.30
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发表时间：
2011
影响因子：
--
通讯作者：
Ierapetritou MG
中科院分区：
文献类型：
--
作者：
Orman MA;Berthiaume F;Androulakis IP;Ierapetritou MG
代谢工程工具已被广泛应用于生物体，以获得对细胞网络的全面了解并改善细胞特性。代谢通量分析（MFA）、通量平衡分析（FBA）和代谢途径分析（MPA）是化学计量网络分析中最流行的工具。尽管在文献中将这些工具应用于众所周知的微生物系统是广泛的，但各种障碍阻止它们在哺乳动物细胞中被利用。有限的实验数据、复杂的调控机制以及对更复杂的营养培养基的需求是哺乳动物细胞系统中的一些主要障碍。然而，哺乳动物细胞已被用于生产治疗性蛋白质，表征疾病状态或相关的异常代谢状况，并分析一些医学上重要的药物的毒理学作用。因此，越来越需要将代谢工程原理扩展到哺乳动物细胞，以了解其潜在的代谢功能。在这篇评论文章中，描述了为化学计量分析开发的先进代谢工程工具，包括MFA、FBA和MPA。详细讨论了这些工具在哺乳动物细胞中的应用，并强调了挑战和机遇。
Metabolic engineering tools have been widely applied to living organisms to gain a comprehensive understanding about cellular networks and to improve cellular properties. Metabolic flux analysis (MFA), flux balance analysis (FBA), and metabolic pathway analysis (MPA) are among the most popular tools in stoichiometric network analysis. Although application of these tools into well-known microbial systems is extensive in the literature, various barriers prevent them from being utilized in mammalian cells. Limited experimental data, complex regulatory mechanisms, and the requirement of more complex nutrient media are some major obstacles in mammalian cell systems. However, mammalian cells have been used to produce therapeutic proteins, to characterize disease states or related abnormal metabolic conditions, and to analyze the toxicological effects of some medicinally important drugs. Therefore, there is a growing need for extending metabolic engineering principles to mammalian cells in order to understand their underlying metabolic functions. In this review article, advanced metabolic engineering tools developed for stoichiometric analysis including MFA, FBA, and MPA are described. Applications of these tools in mammalian cells are discussed in detail, and the challenges and opportunities are highlighted.