Manchester Centre for Integrative Systems Biology, Manchester Interdisciplinary Biocentre, 131 Princess Street, Manchester M1 7DN, UK.
Biochem Soc Trans. 2010 Oct;38(5):1225-9. doi: 10.1042/BST0381225.
Advances in biological techniques have led to the availability of genome-scale metabolic reconstructions for yeast. The size and complexity of such networks impose limits on what types of analyses one can perform. Constraint-based modelling overcomes some of these restrictions by using physicochemical constraints to describe the potential behaviour of an organism. FBA (flux balance analysis) highlights flux patterns through a network that serves to achieve a particular objective and requires a minimal amount of data to make quantitative inferences about network behaviour. Even though FBA is a powerful tool for system predictions, its general formulation sometimes results in unrealistic flux patterns. A typical example is fermentation in yeast: ethanol is produced during aerobic growth in excess glucose, but this pattern is not present in a typical FBA solution. In the present paper, we examine the issue of yeast fermentation against respiration during growth. We have studied a number of hypotheses from the modelling perspective, and novel formulations of the FBA approach have been tested. By making the observation that more respiration requires the synthesis of more mitochondria, an energy cost related to mitochondrial synthesis is added to the FBA formulation. Results, although still approximate, are closer to experimental observations than earlier FBA analyses, at least on the issue of fermentation.
生物技术的进步使得大规模酵母基因组代谢重建成为可能。这些网络的规模和复杂性限制了人们可以进行的分析类型。基于约束的建模通过使用物理化学约束来描述生物体的潜在行为，克服了这些限制。FBA（通量平衡分析）突出了通过网络的通量模式，这些模式有助于实现特定的目标，并需要最少的数据来对网络行为进行定量推断。尽管 FBA 是系统预测的有力工具，但它的一般形式有时会导致不现实的通量模式。一个典型的例子是酵母中的发酵：在过量葡萄糖的有氧生长过程中会产生乙醇，但在典型的 FBA 解决方案中不存在这种模式。在本文中，我们研究了酵母在生长过程中呼吸与发酵的问题。我们从建模的角度研究了一些假设，并测试了 FBA 方法的新公式。通过观察到更多的呼吸需要合成更多的线粒体，因此在 FBA 公式中添加了与线粒体合成相关的能量成本。结果虽然仍然是近似的，但与早期的 FBA 分析相比，更接近实验观察结果，至少在发酵问题上是这样。
