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

细胞代谢代表了将代谢物转化为生命所需分子的酶促反应和运输过程的集合。通常，酶在功能途径的背景下作为集体系统操作。最近的研究表明，这些途径通过形成亚细胞区室或蛋白质复合物表现出高度的空间组织。这种组织提供了一种机制，将底物从一种酶"引导"到另一种酶，从而增加产物产率和反应效率。通过在途径内空间协调酶，有机会将通道的潜在益处转化为目前代谢工程所针对的许多应用。在一个新的和多学科的方法相结合的生物信息学与计算机模拟，我们建议系统地确定所需的条件，通道操作和提高途径的性能。通过预测最有可能受益于沟道效应的反应，这一知识将被用来更有效地设计合成途径。

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.