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Stochastic reaction–diffusion simulation of enzyme compartmentalization reveals improved catalytic efficiency for a synthetic metabolic pathway

Paper ID Volume ID Publish Year Pages File Format Full-Text
31970 44862 2007 9 PDF Available
Title
Stochastic reaction–diffusion simulation of enzyme compartmentalization reveals improved catalytic efficiency for a synthetic metabolic pathway
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.

Keywords
Compartmentalization; In silico predictions; Metabolic channeling; Metabolic flux analysis; Metabolic pathway engineering; Metabolon; Propanediol; Stochastic simulation
First Page Preview
Stochastic reaction–diffusion simulation of enzyme compartmentalization reveals improved catalytic efficiency for a synthetic metabolic pathway
Publisher
Database: Elsevier - ScienceDirect
Journal: Metabolic Engineering - Volume 9, Issue 4, July 2007, Pages 355–363
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering