Departament de Ciències Mèdiques Bàsiques, Institut de Recerca Biomèdica de Lleida (IRBLLEIDA), University of Lleida, Montserrat Roig, 2, 25008 Lleida, Spain.
J Biotechnol. 2010 Sep 1;149(3):141-53. doi: 10.1016/j.jbiotec.2010.01.026. Epub 2010 Feb 10.
Cells are natural factories that can adapt to changes in external conditions. Their adaptive responses to specific stress situations are a result of evolution. In theory, many alternative sets of coordinated changes in the activity of the enzymes of each pathway could allow for an appropriate adaptive readjustment of metabolism in response to stress. However, experimental and theoretical observations show that actual responses to specific changes follow fairly well defined patterns that suggest an evolutionary optimization of that response. Thus, it is important to identify functional effectiveness criteria that may explain why certain patterns of change in cellular components and activities during adaptive response have been preferably maintained over evolutionary time. Those functional effectiveness criteria define sets of physiological requirements that constrain the possible adaptive changes and lead to different operation principles that could explain the observed response. Understanding such operation principles can also facilitate biotechnological and metabolic engineering applications. Thus, developing methods that enable the analysis of cellular responses from the perspective of identifying operation principles may have strong theoretical and practical implications. In this paper we present one such method that was designed based on nonlinear global optimization techniques. Our methodology can be used with a special class of nonlinear kinetic models known as GMA models and it allows for a systematic characterization of the physiological requirements that may underlie the evolution of adaptive strategies.
细胞是天然的工厂，可以适应外部条件的变化。它们对特定应激情况的适应性反应是进化的结果。从理论上讲，每种途径的酶活性的许多替代的协调变化集可以允许代谢以适当的适应性方式对压力进行重新调整。然而，实验和理论观察表明，实际对特定变化的反应遵循相当明确的模式，这表明该反应已经过进化优化。因此，确定功能有效性标准非常重要，这些标准可以解释为什么在适应反应过程中细胞成分和活性的某些变化模式在进化过程中一直得到更好地保持。这些功能有效性标准定义了一组生理需求，这些需求限制了可能的适应性变化，并导致不同的操作原理，可以解释观察到的反应。理解这些操作原理也可以促进生物技术和代谢工程应用。因此，开发能够从识别操作原理的角度分析细胞反应的方法可能具有很强的理论和实际意义。在本文中，我们提出了一种这样的方法，该方法基于非线性全局优化技术设计。我们的方法可以与一类特殊的非线性动力学模型（称为 GMA 模型）一起使用，并且可以系统地表征可能构成适应性策略进化基础的生理需求。
