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

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...

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Main Authors: Yousuke Nishio, Yoshihiro Usuda, Kazuhiko Matsui, Hiroyuki Kurata
Format: Article
Language:English
Published: Springer Nature 2008-01-01
Series:Molecular Systems Biology
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Online Access:https://doi.org/10.1038/msb4100201
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author Yousuke Nishio
Yoshihiro Usuda
Kazuhiko Matsui
Hiroyuki Kurata
author_facet Yousuke Nishio
Yoshihiro Usuda
Kazuhiko Matsui
Hiroyuki Kurata
author_sort Yousuke Nishio
collection DOAJ
description 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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institution Kabale University
issn 1744-4292
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series Molecular Systems Biology
spelling doaj-art-2a1571b227b94064b8ada5fe00bfcc9c2025-08-24T12:01:40ZengSpringer NatureMolecular Systems Biology1744-42922008-01-014111210.1038/msb4100201Computer‐aided rational design of the phosphotransferase system for enhanced glucose uptake in Escherichia coliYousuke Nishio0Yoshihiro Usuda1Kazuhiko Matsui2Hiroyuki Kurata3Fermentation and Biotechnology Laboratories, Ajinomoto Co. Inc.Fermentation and Biotechnology Laboratories, Ajinomoto Co. Inc.Fermentation and Biotechnology Laboratories, Ajinomoto Co. Inc.Department of Bioscience and Bioinformatics, Kyushu Institute of TechnologyAbstract 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.https://doi.org/10.1038/msb4100201Escherichia coliglucose uptakephosphotransferase systemregulationsystem analysis
spellingShingle Yousuke Nishio
Yoshihiro Usuda
Kazuhiko Matsui
Hiroyuki Kurata
Computer‐aided rational design of the phosphotransferase system for enhanced glucose uptake in Escherichia coli
Molecular Systems Biology
Escherichia coli
glucose uptake
phosphotransferase system
regulation
system analysis
title Computer‐aided rational design of the phosphotransferase system for enhanced glucose uptake in Escherichia coli
title_full Computer‐aided rational design of the phosphotransferase system for enhanced glucose uptake in Escherichia coli
title_fullStr Computer‐aided rational design of the phosphotransferase system for enhanced glucose uptake in Escherichia coli
title_full_unstemmed Computer‐aided rational design of the phosphotransferase system for enhanced glucose uptake in Escherichia coli
title_short Computer‐aided rational design of the phosphotransferase system for enhanced glucose uptake in Escherichia coli
title_sort computer aided rational design of the phosphotransferase system for enhanced glucose uptake in escherichia coli
topic Escherichia coli
glucose uptake
phosphotransferase system
regulation
system analysis
url https://doi.org/10.1038/msb4100201
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