Stochastic reaction–diffusion simulation of partmentalization.pdf
Metabolic Engineering 9 (2007) 355–363 Stochastic reaction–diffusion simulation of partmentalization reveals improved catalytic ef?ciency for a synthetic metabolic pathway Robert J. Conrado, Thomas J. Mansell, Jeffrey D. Varner, Matthew P. DeLisa ? School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY 14853, USA Received 18 February 2007; received in revised form 27 April 2007; accepted 4 May 2007 Available online 26 May 2007 Abstract We have demonstrated the accuracy of a spatial stochastic model of Escherichia coli central carbon metabolism using the next subvolume method (NSM), an ef?cient implementation of the Gillespie direct method of stochastic simulation. Using this model, we demonstrate partmentalization of the prising an engineered pathway for biosynthesis of R-1,2-propanediol leads to improved ic properties for the pathway enzymes, especially when substrate diffusivities are low. Our results suggest that partmentalization 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 ef?ciency, 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 event
Stochastic reaction–diffusion simulation of partmentalization 来自淘豆网www.taodocs.com转载请标明出处.