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Updated: Jul 14, 2026

Unraveling Entropic Rate Acceleration Induced by Solvent Dynamics in Membrane Enzymes
Published on: January 16, 2016
Stochastic reaction-diffusion simulation of enzyme compartmentalization reveals improved catalytic efficiency for a
Robert J Conrado1, Thomas J Mansell, Jeffrey D Varner
1School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY 14853, USA.
Abstract:
We have demonstrated the accuracy of a spatial stochastic model of Escherichia coli central carbon metabolism using the next subvolume method (NSM), an efficient implementation of the Gillespie direct method of stochastic simulation. Using this model, we demonstrate that compartmentalization of the enzymes comprising an engineered pathway for biosynthesis of R-1,2-propanediol leads to improved kinetic properties for the pathway enzymes, especially when substrate diffusivities are low. Our results suggest that enzyme compartmentalization is a powerful approach for improving the catalytic turnover of a channeled carbon substrate and should be particularly useful when applied to synthetic metabolic pathways that suffer from poor translation efficiency, are present in highly variable copy numbers, and have low turnover for new substrates. Furthermore, this approach represents a generic modeling framework for simultaneously analyzing spatial and stochastic events in cellular metabolism and should enable quantitative evaluation of the effect of enzyme compartmentalization on virtually any recombinant pathway.
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