Enzyme clustering accelerates processing of intermediates through metabolic channeling

Michele Castellana, Maxwell Z. Wilson, Yifan Xu, Preeti Joshi, Ileana M. Cristea, Joshua D. Rabinowitz, Zemer Gitai, Ned S. Wingreen

Research output: Contribution to journalArticle

171 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1011-1018
Number of pages8
JournalNature biotechnology
Volume32
Issue number10
DOIs
StatePublished - Oct 1 2014

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Molecular Medicine
  • Biomedical Engineering

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