代谢流量比率分析及其在代谢工程中的应用

Application of metabolic flux ratio analysis in metabolic engineering–a review

摘要:

细胞内代谢反应流量在系统理解细胞代谢特性和指导代谢工程改造等方面都起着重要的作用。由于代谢流量难以直接测量得到, 在很多情况下通过跟踪稳定同位素在代谢网络中的转移并进行相应的模型计算能有效地定量代谢流量。代谢流量比率分析法能够高度体现系统的生物化学真实性、辨别细胞代谢网络的拓扑结构, 并且能够相对简单快速地定量反应速率等, 因此受到代谢工程研究者越来越多的重视。以下着重介绍并讨论了利用代谢物同位体分布信息分析关键代谢节点合成途径的流量比率、基于流量比率的代谢流量解析、以及应用于代谢工程等的相关原理、实验测量、数据分析、使用条件等, 以期充分发挥代谢流量比率分析法的优势, 并将其拓展推广至更多细胞体系的代谢特性阐明和代谢工程改造中去。

Abstract:

Intracellular metabolic fluxes are important to understand metabolic characteristics of cells and to direct metabolic engineering strategies. Because intracellular fluxes cannot be directly assessed, isotope experiments are usually conducted to trace metabolic fluxes. The flux-ratio analysis can reflect high biochemical veracity, be employed to identify the topology of the networks, and offer greatly reduced computational expense for flux determination. In order to apply this metabolic analysis method to better elucidate more cell systems, we discussed in this study the principles, experiments and assays, data interpretation, and other issues that should be considered in flux ratio determination, metabolic flux quantification and its metabolic engineering applications.