Schilling C H, Schuster S, Palsson B O, Heinrich R
Department of Bioengineering, University of California, San Diego, La Jolla, California 92093-0412, USA.
Biotechnol Prog. 1999 May-Jun;15(3):296-303. doi: 10.1021/bp990048k.
This article reviews the relatively short history of metabolic pathway analysis. Computer-aided algorithms for the synthesis of metabolic pathways are discussed. Important algebraic concepts used in pathway analysis, such as null space and convex cone, are explained. It is demonstrated how these concepts can be translated into meaningful metabolic concepts. For example, it is shown that the simplest vectors spanning the region of all admissible fluxes in stationary states, for which the term elementary flux modes was coined, correspond to fundamental pathways in the system. The concepts are illustrated with the help of a reaction scheme representing the glyoxylate cycle and adjacent reactions of aspartate and glutamate synthesis. The interrelations between pathway analysis and metabolic control theory are outlined. Promising applications for genome annotation and for biotechnological purposes are discussed. Armed with a better understanding of the architecture of cellular metabolism and the enormous amount of genomic data available today, biochemists and biotechnologists will be able to draw the entire metabolic map of a cell and redesign it by rational and directed metabolic engineering.
本文回顾了代谢途径分析相对较短的历史。讨论了用于合成代谢途径的计算机辅助算法。解释了途径分析中使用的重要代数概念，如零空间和凸锥。展示了这些概念如何转化为有意义的代谢概念。例如，结果表明，用于生成“基本通量模式”这一术语的、跨越稳态下所有允许通量区域的最简单向量，对应于系统中的基本途径。借助代表乙醛酸循环以及天冬氨酸和谷氨酸合成的相邻反应的反应方案对这些概念进行了说明。概述了途径分析与代谢控制理论之间的相互关系。讨论了在基因组注释和生物技术目的方面的有前景的应用。有了对细胞代谢结构和当今可用的大量基因组数据的更好理解，生物化学家和生物技术专家将能够绘制出细胞的完整代谢图谱，并通过合理且定向的代谢工程对其进行重新设计。
