Analysis of l-glutamic acid fermentation by using a dynamic metabolic simulation model of Escherichia coli

Yousuke Nishio, Soichi Ogishima, Masao Ichikawa, Yohei Yamada, Yoshihiro Usuda, Tadashi Masuda, Hiroshi Tanaka

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

Background: Understanding the process of amino acid fermentation as a comprehensive system is a challenging task. Previously, we developed a literature-based dynamic simulation model, which included transcriptional regulation, transcription, translation, and enzymatic reactions related to glycolysis, the pentose phosphate pathway, the tricarboxylic acid (TCA) cycle, and the anaplerotic pathway of Escherichia coli. During simulation, cell growth was defined such as to reproduce the experimental cell growth profile of fed-batch cultivation in jar fermenters. However, to confirm the biological appropriateness of our model, sensitivity analysis and experimental validation were required. Results: We constructed an l-glutamic acid fermentation simulation model by removing sucAB, a gene encoding α-ketoglutarate dehydrogenase. We then performed systematic sensitivity analysis for l-glutamic acid production; the results of this process corresponded with previous experimental data regarding l-glutamic acid fermentation. Furthermore, it allowed us to predicted the possibility that accumulation of 3-phosphoglycerate in the cell would regulate the carbon flux into the TCA cycle and lead to an increase in the yield of l-glutamic acid via fermentation. We validated this hypothesis through a fermentation experiment involving a model l-glutamic acid-production strain, E. coli MG1655 ΔsucA in which the phosphoglycerate kinase gene had been amplified to cause accumulation of 3-phosphoglycerate. The observed increase in l-glutamic acid production verified the biologically meaningful predictive power of our dynamic metabolic simulation model. Conclusions: In this study, dynamic simulation using a literature-based model was shown to be useful for elucidating the precise mechanisms involved in fermentation processes inside the cell. Further exhaustive sensitivity analysis will facilitate identification of novel factors involved in the metabolic regulation of amino acid fermentation.

Original languageEnglish
Article number92
JournalBMC Systems Biology
Volume7
DOIs
Publication statusPublished - 2013 Sep 22

Keywords

  • Dynamic metabolic simulation
  • Escherichia coli
  • Phosphoglycerate kinase
  • Sensitivity analysis
  • l-glutamic acid fermentation

ASJC Scopus subject areas

  • Structural Biology
  • Modelling and Simulation
  • Molecular Biology
  • Computer Science Applications
  • Applied Mathematics

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