A combined theoretical and experimental approach to the study of metabolic channeling

细胞新陈代谢是将代谢产物转化为生命所需分子的一系列酶反应和运输过程。通常情况下，酶在功能途径的背景下作为一个集体系统运行。最近的研究表明，这些途径无论是通过亚细胞室的形成还是通过蛋白质复合体的形成，都表现出高度的空间组织性。这种组织提供了一种将底物从一种酶‘引导’到另一种酶的机制，从而提高了产物产量和反应效率。通过在途径内对酶进行空间协调，有机会将引导到代谢工程目前目标的许多应用中的潜在好处转化为潜在的好处。在一种将生物信息学和计算机模拟相结合的新的多学科方法中，我们建议系统地识别通道运行所需的条件，并改善通路性能。通过预测最有可能从导流中受益的反应，这些知识将被利用来更有效地设计合成路径。

Cellular metabolism represents a collection of enzymatic reactions and transport processes that convert metabolites into the molecules required for life. Typically enzymes operate as a collective system within the context of functional pathways. Recent studies have revealed that these pathways exhibit a high degree of spatial organization either through the formation of sub-cellular compartments or protein complexes. Such organization provides a mechanism to 'channel' a substrate from one enzyme to another, increasing product yield and reaction efficiency. Through spatially coordinating enzymes within pathways, there is an opportunity to translate the potential benefits of channeling to many applications currently being targeted by metabolic engineering. In a novel and multi-disciplinary approach combining bioinformatics with computer simulations, we propose to systematically identify the conditions required for channeling to operate and improve pathway performance. By predicting reactions which are most likely to benefit from channeling, this knowledge will be exploited to design synthetic pathways more effectively.