A Fermentation State Marker Rule Design Task in Metabolic Engineering

Egils Stalidzans (Corresponding Author), Reinis Muiznieks, Konstantins Dubencovs, Elina Sile, Kristaps Berzins, Arturs Suleiko, Juris Vanags

Research output: Contribution to journalArticlepeer-review

Abstract

There are several ways in which mathematical modeling is used in fermentation control, but mechanistic mathematical genome-scale models of metabolism within the cell have not been applied or implemented so far. As part of the metabolic engineering task setting, we propose that metabolite fluxes and/or biomass growth rate be used to search for a fermentation steady state marker rule. During fermentation, the bioreactor control system can automatically detect the desired steady state using a logical marker rule. The marker rule identification can be also integrated with the production growth coupling approach, as presented in this study. A design of strain with marker rule is demonstrated on genome scale metabolic model iML1515 of Escherichia coli MG1655 proposing two gene deletions enabling a measurable marker rule for succinate production using glucose as a substrate. The marker rule example at glucose consumption 10.0 is: IF (specific growth rate μ is above 0.060 h−1, AND CO2 production under 1.0, AND ethanol production above 5.5), THEN succinate production is within the range 8.2–10, where all metabolic fluxes units are mmol ∗ gDW−1 ∗ h−1. An objective function for application in metabolic engineering, including productivity features and rule detecting sensor set characterizing parameters, is proposed. Two-phase approach to implementing marker rules in the cultivation control system is presented to avoid the need for a modeler during production.

Original languageEnglish
Article number1427
JournalBioengineering
Volume10
Issue number12
DOIs
Publication statusPublished - Dec 2023
Externally publishedYes

Keywords*

  • genome scale metabolic model
  • growth coupling
  • marker rule
  • metabolic engineering
  • production envelope

Field of Science*

  • 3.2 Clinical medicine
  • 2.6 Medical engineering
  • 2.4 Chemical engineering

Publication Type*

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database

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