Enzyme clustering accelerates processing of intermediates through metabolic channeling

Nat Biotechnol. 2014 Oct;32(10):1011-8. doi: 10.1038/nbt.3018. Epub 2014 Sep 28.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Arginine / metabolism
  • Computational Biology
  • Enzymes* / metabolism
  • Enzymes* / physiology
  • Escherichia coli Proteins* / metabolism
  • Escherichia coli Proteins* / physiology
  • Escherichia coli* / enzymology
  • Escherichia coli* / metabolism
  • Escherichia coli* / physiology
  • Homeostasis
  • Metabolic Networks and Pathways / physiology*
  • Models, Biological
  • Pyrimidines / metabolism

Substances

  • Enzymes
  • Escherichia coli Proteins
  • Pyrimidines
  • Arginine
  • pyrimidine