Hoefnagel, Starrenburg, Martens, Hugenholtz, Kleerebezem, Van Swam, Bongers, Westerhoff, Snoep, 2002

Model Status

This is the original unchecked version of the model imported from the previous CellML model repository, 24-Jan-2006.

Model Structure

Frequently, the microorganisms which are used in biotech industries to manufacture valuable compounds such as drugs, fuels, and fibres, are not naturally optimised for maximum production. In bioengineering, one frequent aim is to maximise the flux through a particular pathway. However, due to the complex, branching nature of metabolic networks, increasing metabolic flux can be difficult.

Traditionally, metabolic control analysis (MCA) has been used to identify the specific enzymes that have the most control over the metabolic flux. In MCA, enzymes are assigned a flux control coefficient. This value quantifies the influence of a particular enzyme on overall metabolic flux. However, the alleviation of rate-limiting steps, by increasing the concentration of enzymes with a high flux control coefficient, is not always successful in increasing metabolic flux.

In the Hoefnagel et al. 2002 model described here, the authors demonstrate that an integrated approach of kinetic modelling, MCA, and experimental analysis can be used to successfully model pyruvate distribution in the bacterium Lactococcus lactis. Lactic acid bacteria are used in milk fermentation, the main product of which is lactate (see the figure below). For dairy products such as butter, diacetyl produced by Lactococcus lactis is a flavour component. Naturally, diacetyl is only produced in small quantities, and butter manufacturers try to optimise its production. A combined approach to metabolic engineering identified the enzymes with the greatest effect on metabolic flux. In turn, this highlighted which genes should be targeted in the genetic engineering of the model organism in order to maximise metabolic output.

Metabolic engineering of lactic acid bacteria, the combined approach: kinetic modelling, metabolic control and experimental analysis, Marcel H.N. Hoefnagel, Marjo J.C. Starrenburg, Dirk E. Martens, Jeroen Hugenholtz, Michiel Kleerebezem, Iris I. Van Swam, Roger Bongers, Hans V. Westerhoff, and Jacky L. Snoep, 2002, Microbiology , 148, 1003-1013. (Full text (HTML) and PDF versions of the article are available to subscribers on the Microbiology website.) PubMed ID: 11932446

A schematic diagram of the reactions included in the model to describe the distribution of carbon from pyruvate in L. lactis.