Carlson Ross P
Department of Chemical and Biological Engineering, Center for Biofilm Engineering, Montana State University, Bozeman, MT 59717, USA.
Bioinformatics. 2007 May 15;23(10):1258-64. doi: 10.1093/bioinformatics/btm082. Epub 2007 Mar 7.
Interpretation of bioinformatics data in terms of cellular function is a major challenge facing systems biology. This question is complicated by robust metabolic networks filled with structural features like parallel pathways and isozymes. Under conditions of nutrient sufficiency, metabolic networks are well known to be regulated for thermodynamic efficiency however; efficient biochemical pathways are anabolically expensive to construct. While parameters like thermodynamic efficiency have been extensively studied, a systems-based analysis of anabolic proteome synthesis 'costs' and the cellular function implications of these costs has not been reported.
A cost-benefit analysis of an in silico Escherichia coli network revealed the relationship between metabolic pathway proteome synthesis requirements, DNA-coding sequence length, thermodynamic efficiency and substrate affinity. The results highlight basic metabolic network design principles. Pathway proteome synthesis requirements appear to have shaped biochemical network structure and regulation. Under conditions of nutrient scarcity and other general stresses, E. coli expresses pathways with relatively inexpensive proteome synthesis requirements instead of more efficient but also anabolically more expensive pathways. This evolutionary strategy provides a cellular function-based explanation for common network motifs like isozymes and parallel pathways and possibly explains 'overflow' metabolisms observed during nutrient scarcity.
Supplementary data are available at Bioinformatics online.
从细胞功能角度解释生物信息学数据是系统生物学面临的一项重大挑战。充满平行途径和同工酶等结构特征的稳健代谢网络使这个问题变得复杂。然而，在营养充足的条件下，众所周知代谢网络会为了热力学效率而受到调控；高效的生化途径构建起来在合成代谢方面成本高昂。虽然像热力学效率这样的参数已经得到了广泛研究，但尚未有基于系统的对合成代谢蛋白质组合成“成本”以及这些成本对细胞功能的影响的分析报告。
对一个计算机模拟的大肠杆菌网络进行的成本效益分析揭示了代谢途径蛋白质组合成需求、DNA编码序列长度、热力学效率和底物亲和力之间的关系。结果突出了基本的代谢网络设计原则。途径蛋白质组合成需求似乎塑造了生化网络的结构和调控。在营养稀缺和其他一般应激条件下，大肠杆菌表达蛋白质组合成需求相对较低的途径，而不是更高效但在合成代谢方面也更昂贵的途径。这种进化策略为同工酶和平行途径等常见网络基序提供了基于细胞功能的解释，并且可能解释了在营养稀缺期间观察到的“溢流”代谢。
补充数据可在《生物信息学》在线获取。
