Applied Microbiology and Biotechnology

, Volume 97, Issue 19, pp 8729–8739 | Cite as

Genome-scale metabolic model for Lactococcus lactis MG1363 and its application to the analysis of flavor formation

  • Nicolas A. L. Flahaut
  • Anne Wiersma
  • Bert van de Bunt
  • Dirk E. Martens
  • Peter J. Schaap
  • Lolke Sijtsma
  • Vitor A. Martins dos Santos
  • Willem M. de Vos
Applied microbial and cell physiology


Lactococcus lactis subsp. cremoris MG1363 is a paradigm strain for lactococci used in industrial dairy fermentations. However, despite of its importance for process development, no genome-scale metabolic model has been reported thus far. Moreover, current models for other lactococci only focus on growth and sugar degradation. A metabolic model that includes nitrogen metabolism and flavor-forming pathways is instrumental for the understanding and designing new industrial applications of these lactic acid bacteria. A genome-scale, constraint-based model of the metabolism and transport in L. lactis MG1363, accounting for 518 genes, 754 reactions, and 650 metabolites, was developed and experimentally validated. Fifty-nine reactions are directly or indirectly involved in flavor formation. Flux Balance Analysis and Flux Variability Analysis were used to investigate flux distributions within the whole metabolic network. Anaerobic carbon-limited continuous cultures were used for estimating the energetic parameters. A thorough model-driven analysis showing a highly flexible nitrogen metabolism, e.g., branched-chain amino acid catabolism which coupled with the redox balance, is pivotal for the prediction of the formation of different flavor compounds. Furthermore, the model predicted the formation of volatile sulfur compounds as a result of the fermentation. These products were subsequently identified in the experimental fermentations carried out. Thus, the genome-scale metabolic model couples the carbon and nitrogen metabolism in L. lactis MG1363 with complete known catabolic pathways leading to flavor formation. The model provided valuable insights into the metabolic networks underlying flavor formation and has the potential to contribute to new developments in dairy industries and cheese-flavor research.


Genome-scale Constraint-based model Metabolic network Lactococcus lactis Flavors Chemostat culture 

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Nicolas A. L. Flahaut
    • 1
    • 2
    • 4
    • 7
  • Anne Wiersma
    • 1
    • 3
  • Bert van de Bunt
    • 1
    • 3
  • Dirk E. Martens
    • 6
  • Peter J. Schaap
    • 1
    • 2
    • 7
  • Lolke Sijtsma
    • 1
    • 4
    • 5
  • Vitor A. Martins dos Santos
    • 7
  • Willem M. de Vos
    • 2
    • 8
  1. 1.Top Institute Food and Nutrition (TIFN)WageningenThe Netherlands
  2. 2.Laboratory of MicrobiologyWageningen UniversityWageningenThe Netherlands
  3. 3.NIZO food research BVEdeThe Netherlands
  4. 4.Kluyver Centre for Genomics of Industrial Fermentation/NCSBDelftThe Netherlands
  5. 5.Wageningen UR Food & Biobased ResearchWageningenThe Netherlands
  6. 6.Food and Bioprocess Engineering GroupWageningen UniversityWageningenThe Netherlands
  7. 7.Laboratory of Systems and Synthetic BiologyWageningen UniversityWageningenThe Netherlands
  8. 8.Department of Veterinary Biosciences and Department of Bacteriology & ImmunologyUniversity of HelsinkiHelsinkiFinland

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