Metabolic flux analysis and pharmaceutical production

Metabolic flux analysis and pharmaceutical production
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DOI:
10.1016/j.ymben.2009.10.004
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发表时间:
2010-03-01
影响因子:
8.4
通讯作者:
Pfeifer, Blaine A.
Pfeifer, Blaine A.
中科院分区:
工程技术1区
文献类型:
--
作者:
Boghigian, Brett A.;Seth, Gargi;Pfeifer, Blaine A.

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生物系统的合理工程是一个固有的复杂过程,由于其进化的性质。代谢工程在过去的20年中出现并发展成为一个领域,其中生物系统的合理工程方法现在被应用于特定的工业,医学或科学问题。相当感兴趣的是细胞本身内代谢通量的测定,称为代谢通量分析。这期特刊和这篇综述特别关注代谢通量分析在改善药物生产过程(小分子和大分子)中的应用。虽然代谢通量分析在药物生产的应用中受到一定的限制,但总体目标是:(1)更好地了解所讨论的生物体和/或过程,以及(2)为进一步设计(在代谢和过程规模上)改善这些生物体中的药物生产提供合理的基础。这篇综述文章的重点是介绍代谢通量分析的实验和计算方法是如何成熟的,反映了代谢工程领域本身的成熟,同时突出了一些成功的应用对小分子和大分子药物。(C)2009 Elsevier Inc. All rights reserved.
Rational engineering of biological systems is an inherently complex process due to their evolved nature. Metabolic engineering emerged and developed over the past 20 years as a field in which methodologies for the rational engineering of biological systems is now being applied to specific industrial, medical, or scientific problems. Of considerable interest is the determination of metabolic fluxes within the cell itself, called metabolic flux analysis. This special issue and this review have a particular interest in the application of metabolic flux analysis for improving the pharmaceutical production process (for both small and large molecules). Though metabolic flux analysis has been somewhat limited in application towards pharmaceutical production, the overall goal is to: (1) have a better understanding of the organism and/or process in question, and (2) provide a rational basis to further engineer (on both metabolic and process scales) improved pharmaceutical production in these organisms. The focus of this review article is to present how experimental and computational methods of metabolic flux analysis have matured, mirroring the maturation of the metabolic engineering field itself, while highlighting some of the successful applications towards both small- and large-molecule pharmaceuticals. (C) 2009 Elsevier Inc. All rights reserved.