Computer-aided rational design of the phosphotransferase system for enhanced glucose uptake in Escherichia coli

Molecular Systems Biology
Yousuke NishioHiroyuki Kurata

Abstract

The phosphotransferase system (PTS) is the sugar transportation machinery that is widely distributed in prokaryotes and is critical for enhanced production of useful metabolites. To increase the glucose uptake rate, we propose a rational strategy for designing the molecular architecture of the Escherichia coli glucose PTS by using a computer-aided design (CAD) system and verified the simulated results with biological experiments. CAD supports construction of a biochemical map, mathematical modeling, simulation, and system analysis. Assuming that the PTS aims at controlling the glucose uptake rate, the PTS was decomposed into hierarchical modules, functional and flux modules, and the effect of changes in gene expression on the glucose uptake rate was simulated to make a rational strategy of how the gene regulatory network is engineered. Such design and analysis predicted that the mlc knockout mutant with ptsI gene overexpression would greatly increase the specific glucose uptake rate. By using biological experiments, we validated the prediction and the presented strategy, thereby enhancing the specific glucose uptake rate.

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Citations

Oct 18, 2011·Nature Chemical Biology·Christopher D DoucetteJoshua D Rabinowitz
Feb 2, 2010·DNA Research : an International Journal for Rapid Publication of Reports on Genes and Genomes·Gustavo EydallinJavier Pozueta-Romero
Dec 18, 2010·Journal of Theoretical Biology·Kazuhiro Maeda, Hiroyuki Kurata
Dec 18, 2008·The FEBS Journal·Andreas KremlingKatja Bettenbrock
Jun 23, 2016·Microbial Cell Factories·Nusrat JahanHiroyuki Kurata
Sep 24, 2015·PLoS Computational Biology·Vipin NarangChristopher Monterola
May 27, 2009·Bioinformatics·Quanyu Zhao, Hiroyuki Kurata
Jul 31, 2013·Briefings in Bioinformatics·Hiroyuki KurataTakenori Takata
Jul 18, 2008·Bioprocess and Biosystems Engineering·Emi ShiraishiHiroyuki Kurata
Jan 1, 2012·Metabolites·Andreas KremlingKatja Bettenbrock
Mar 13, 2015·Applied Microbiology and Biotechnology·Lothar Eggeling, Michael Bott
Jul 24, 2012·Bioprocess and Biosystems Engineering·Kazuhiro MaedaHiroyuki Kurata
Nov 22, 2019·Scientific Reports·Hiroyuki Kurata
May 7, 2020·Pflügers Archiv : European journal of physiology·Jean-Marc Jeckelmann, Bernhard Erni

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Methods Mentioned

BETA
environmental stresses
phosphotransferase
electrophoresis
genetic modifications
PCR
ELISA

Software Mentioned

CADLIVE
EcoCyc

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