Applied Microbiology and Biotechnology

, Volume 103, Issue 7, pp 3153–3165 | Cite as

A genome-scale metabolic network of the aroma bacterium Leuconostoc mesenteroides subsp. cremoris

  • Emrah Özcan
  • S. Selvin Selvi
  • Emrah Nikerel
  • Bas Teusink
  • Ebru Toksoy Öner
  • Tunahan ÇakırEmail author
Applied microbial and cell physiology


Leuconostoc mesenteroides subsp. cremoris is an obligate heterolactic fermentative lactic acid bacterium that is mostly used in industrial dairy fermentations. The phosphoketolase pathway (PKP) is a unique feature of the obligate heterolactic fermentation, which leads to the production of lactate, ethanol, and/or acetate, and the final product profile of PKP highly depends on the energetics and redox state of the organism. Another characteristic of the L. mesenteroides subsp. cremoris is the production of aroma compounds in dairy fermentation, such as in cheese production, through the utilization of citrate. Considering its importance in dairy fermentation, a detailed metabolic characterization of the organism is necessary for its more efficient use in the industry. To this aim, a genome-scale metabolic model of dairy-origin L. mesenteroides subsp. cremoris ATCC 19254 (iLM.c559) was reconstructed to explain the energetics and redox state mechanisms of the organism in full detail. The model includes 559 genes governing 1088 reactions between 1129 metabolites, and the reactions cover citrate utilization and citrate-related flavor metabolism. The model was validated by simulating co-metabolism of glucose and citrate and comparing the in silico results to our experimental results. Model simulations further showed that, in co-metabolism of citrate and glucose, no flavor compounds were produced when citrate could stimulate the formation of biomass. Significant amounts of flavor metabolites (e.g., diacetyl and acetoin) were only produced when citrate could not enhance growth, which suggests that flavor formation only occurs under carbon and ATP excess. The effects of aerobic conditions and different carbon sources on product profiles and growth were also investigated using the reconstructed model. The analyses provided further insights for the growth stimulation and flavor formation mechanisms of the organism.


Lactic acid bacteria Leuconostoc mesenteroides subsp. cremoris Heterolactic fermentation Flavor metabolism Genome-scale metabolic model Flux balance analysis 



Burcu Şirin (Yeditepe University) and Sebastián N. Mendoza (VU Amsterdam) are acknowledged for their help in HPLC analyses and reorganizing the SBML file, respectively.

Funding information

This work received financial support from The Scientific and Technological Research Council of Turkey through TUBITAK 2214-A program and the Marmara University Scientific Research Project Fund through Project No: FEN-C-DRP-091116-0498.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Supplementary material

253_2019_9630_MOESM1_ESM.xlsx (839 kb)
ESM 1 (XLSX 838 kb)
253_2019_9630_MOESM2_ESM.pdf (371 kb)
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253_2019_9630_MOESM3_ESM.xml (1.3 mb)
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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of BioengineeringGebze Technical UniversityKocaeliTurkey
  2. 2.IBSB, Department of BioengineeringMarmara UniversityIstanbulTurkey
  3. 3.Systems Bioinformatics, Amsterdam Institute for Molecules, Medicines and SystemsVU AmsterdamAmsterdamThe Netherlands
  4. 4.Genetics and Bioengineering DepartmentYeditepe UniversityIstanbulTurkey

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