Dynamic co-culture metabolic models reveal the fermentation dynamics, metabolic capacities and interplays of cheese starter cultures

Emrah Özcan, Merve Seven, Burcu Şirin, Tunahan Çakır, Emrah Nikerel, Bas Teusink*, Ebru Toksoy Öner

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review


In this study, we have investigated the cheese starter culture as a microbial community through a question: can the metabolic behaviour of a co-culture be explained by the characterized individual organism that constituted the co-culture? To address this question, the dairy-origin lactic acid bacteria Lactococcus lactis subsp. cremoris, Lactococcus lactis subsp. lactis, Streptococcus thermophilus and Leuconostoc mesenteroides, commonly used in cheese starter cultures, were grown in pure and four different co-cultures. We used a dynamic metabolic modelling approach based on the integration of the genome-scale metabolic networks of the involved organisms to simulate the co-cultures. The strain-specific kinetic parameters of dynamic models were estimated using the pure culture experiments and they were subsequently applied to co-culture models. Biomass, carbon source, lactic acid and most of the amino acid concentration profiles simulated by the co-culture models fit closely to the experimental results and the co-culture models explained the mechanisms behind the dynamic microbial abundance. We then applied the co-culture models to estimate further information on the co-cultures that could not be obtained by the experimental method used. This includes estimation of the profile of various metabolites in the co-culture medium such as flavour compounds produced and the individual organism level metabolic exchange flux profiles, which revealed the potential metabolic interactions between organisms in the co-cultures.

Original languageEnglish
Pages (from-to)223-237
Number of pages15
JournalBiotechnology and Bioengineering
Issue number1
Early online date14 Sept 2020
Publication statusPublished - Jan 2021


Frank Bruggeman, Herwig Bachmann, Douwe Molenaar, Brett Olivier, Eunice van Pelt-Kleinjan, Sebasti?n N. Mendoza, Sieze Douwenga, Daan de Groot, Chrats Melkonian and Rinke van Tatenhove-Pel from Systems Biology Lab at VU Amsterdam are acknowledged for their support through discussions and advice. Sebasti?n N. Mendoza also helped in revision of the published metabolic model of S. thermophilus. S. Selvin Selvi from IBSB, Marmara University is acknowledged for her help in the experiments. This study received financial support from The Scientific and Technological Research Council of Turkey through TUBITAK 2211-C and 2214-A program?and the Marmara University Scientific Research Project Fund through Project No: FEN-C-DRP-091116-0498.

FundersFunder number
Marmara University Scientific Research Project FundFEN‐C‐DRP‐091116‐0498
Türkiye Bilimsel ve Teknolojik Araştirma Kurumu
Marmara Üniversitesi


    • co-culture metabolic modelling
    • genome-scale metabolic network
    • lactic acid bacteria
    • starter cultures


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