Enzyme clustering accelerates processing of intermediates through metabolic channeling.
Enzyme clustering accelerates processing of intermediates through metabolic channeling.
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DOI：
10.1038/nbt.3018
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发表时间：
2014-10
影响因子：
46.9
通讯作者：
Wingreen NS
中科院分区：
文献类型：
--
作者：
Castellana M;Wilson MZ;Xu Y;Joshi P;Cristea IM;Rabinowitz JD;Gitai Z;Wingreen NS
我们提出了一个定量模型来证明，coclustering多个酶成紧凑的团聚体加速处理的中间体，产生相同的效率效益直接通道，一个众所周知的机制，其中酶之间的漏斗通过物理隧道的酶活性位点。该模型预测的分离和大小的coclusters，最大限度地提高代谢效率，这种预测是在协议与以前报道的coclusters在哺乳动物细胞之间的间距。为了直接验证，我们研究了大肠杆菌中的代谢分支点，并通过实验证实了模型预测，即酶聚集体可以加速一个分支对共享中间体的处理，从而调节稳态通量划分。我们的研究建立了一个定量的框架，以了解共簇介导的代谢通道及其应用效率的提高和代谢调节。
We present a quantitative model to demonstrate that coclustering multiple enzymes into compact agglomerates accelerates the processing of intermediates, yielding the same efficiency benefits as direct channeling, a well-known mechanism in which enzymes are funneled between enzyme active sites through a physical tunnel. The model predicts the separation and size of coclusters that maximize metabolic efficiency, and this prediction is in agreement with previously reported spacings between coclusters in mammalian cells. For direct validation, we study a metabolic branch point in Escherichia coli and experimentally confirm the model prediction that enzyme agglomerates can accelerate the processing of a shared intermediate by one branch, and thus regulate steady-state flux division. Our studies establish a quantitative framework to understand coclustering-mediated metabolic channeling and its application to both efficiency improvement and metabolic regulation.