期刊
NATURE BIOTECHNOLOGY
卷 32, 期 10, 页码 1011-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nbt.3018
关键词
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资金
- National Science Foundation [PHY-0957573, PHY-1305525, GRFP DGE-1148900]
- US National Institutes of Health [NIDA DP1DA026192, NIAID R21AI102187]
- Human Frontiers Science Program
- NJCCR postdoctoral fellowship
- Direct For Mathematical & Physical Scien
- Division Of Physics [1305525] Funding Source: National Science Foundation
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.
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