Systems Biology of Lactic Acid Bacteria: For Food and Thought
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Lactic acid bacteria (LAB) ferment plants, fish, meats and milk and turn them into tasty food products with increased shelf life; other LAB help digesting food and create a healthy environment in the intestine. The economic and societal importance of these relatively simple and small bacteria is immense. In this review we hope to show that their adaptations to nutrient-rich environments provides fascinating and often puzzling behaviours that give rise to many fundamental evolutionary biological questions in need of a systems biology approach. We will provide examples of such questions, compare the (metabolic) behaviour of LAB to that of other model organisms, and provide the latest insights, if available.
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Recent studies in different microbial species have shown that high growth rates come at the expense of the expression level of metabolic enzymes and/or stress proteins.
“Recent studies in different microbial species have shown that high growth rates come at the expense of the expression level of metabolic enzymes and/or stress proteins [69,83,84].”
From Microbiota of Cheese Ecosystems: A Perspective on Cheesemaking (2025) · cites this paper as [83]
In “Metabolic adaptation to rich nutrient environments: cheating and overflow” (page unavailable), the review describes an E. coli trade-off: at higher growth rates, cells switch from protein-costly, ATP-efficient pathways to cheaper ones. It does not establish reduced expression of metabolic enzymes or stress proteins across different species; it reports that glycolytic enzyme levels in L. lactis remained largely constant as flux increased. (LLM, conf=0.85)
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Cites
Hardin, G. (1968) · Science · doi:10.1126/science.162.3859.1243 · Cited by 25,167 · see citing works
CRISPR Provides Acquired Resistance Against Viruses in Prokaryotes
Barrangou, R., Fremaux, C., Deveau, H., Richards, M., Boyaval, P., Moineau, S., Romero, D. A., & Horvath, P. (2007) · Science · doi:10.1126/science.1138140 · Cited by 6,304 · see citing works
Interdependence of Cell Growth and Gene Expression: Origins and Consequences
Scott, M., Gunderson, C. W., Mateescu, E. M., Zhang, Z., & Hwa, T. (2010) · Science · doi:10.1126/science.1192588 · Cited by 1,470 · see citing works
Metabolic dependencies drive species co-occurrence in diverse microbial communities
Zelezniak, A., Andrejev, S., Ponomarova, O., Mende, D. R., Bork, P., & Patil, K. R. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1421834112 · Cited by 930 · see citing works
Stress Physiology of Lactic Acid Bacteria.
Papadimitriou, K., Alegría, Á., Bron, P. A., de Angelis, M., Gobbetti, M., Kleerebezem, M., Lemos, J. A., Linares, D. M., Ross, P., Stanton, C., et al. (2016) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00076-15 · Cited by 914 · see citing works
Overflow metabolism in Escherichia coli results from efficient proteome allocation
Basan, M., Hui, S., Okano, H., Zhang, Z., Shen, Y., Williamson, J. R., & Hwa, T. (2015) · Nature · doi:10.1038/nature15765 · Cited by 785 · see citing works
Snowdrift game dynamics and facultative cheating in yeast
Gore, J., Youk, H., & van Oudenaarden, A. (2009) · Nature · doi:10.1038/nature07921 · Cited by 653 · see citing works
Shifts in growth strategies reflect tradeoffs in cellular economics
Molenaar, D., van Berlo, R., de Ridder, D., & Teusink, B. (2009) · Molecular Systems Biology · doi:10.1038/msb.2009.82 · Cited by 653 · see citing works
Self-citationDispensable and Indispensable Amino Acids for Humans
Reeds, P. J. (2000) · Journal of Nutrition · doi:10.1093/jn/130.7.1835s · Cited by 511 · see citing works
Genome‐scale models of metabolism and gene expression extend and refine growth phenotype prediction
O'Brien, E. J., Lerman, J. A., Chang, R. L., Hyduke, D. R., & Palsson, B. Ø. (2013) · Molecular Systems Biology · doi:10.1038/msb.2013.52 · Cited by 471 · see citing works
Coordination of bacterial proteome with metabolism by cyclic AMP signalling
You, C., Okano, H., Hui, S., Zhang, Z., Kim, M., Gunderson, C. W., Wang, Y.-P., Lenz, P., Yan, D., & Hwa, T. (2013) · Nature · doi:10.1038/nature12446 · Cited by 432 · see citing works
Amino Acid Catabolic Pathways of Lactic Acid Bacteria
Fernández, M., & Zúñiga, M. (2006) · Critical Reviews in Microbiology · doi:10.1080/10408410600880643 · Cited by 416 · see citing works
A review on Lactococcus lactis: from food to factory
Song, A. A.-L., In, L. L. A., Lim, S. H. E., & Rahim, R. A. (2017) · Microbial Cell Factories · doi:10.1186/s12934-017-0669-x · Cited by 414 · see citing works
The Cost of Protein Production
Kafri, M., Metzl-Raz, E., Jona, G., & Barkai, N. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.12.015 · Cited by 348 · see citing works
Fitness and stability of obligate cross-feeding interactions that emerge upon gene loss in bacteria
Pande, S., Merker, H., Bohl, K., Reichelt, M., Schuster, S., de Figueiredo, L. F., Kaleta, C., & Kost, C. (2013) · The ISME Journal · doi:10.1038/ismej.2013.211 · Cited by 321 · see citing works
Lost in Transition: Start-Up of Glycolysis Yields Subpopulations of Nongrowing Cells
van Heerden, J. H., Wortel, M. T., Bruggeman, F. J., Heijnen, J. J., Bollen, Y. J. M., Planqué, R., Hulshof, J., O’Toole, T. G., Wahl, A., & Teusink, B. (2014) · Science · doi:10.1126/science.1245114 · Cited by 299 · see citing works
Self-citationTeusink, B., Wiersma, A., Douwe Molenaar, B., Francke, C., de Vos, W. M., Siezen, R. J., & Smid, E. J. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m606263200 · Cited by 283 · see citing works
Self-citationPhosphoribosyl Diphosphate (PRPP): Biosynthesis, Enzymology, Utilization, and Metabolic Significance
Hove‐Jensen, B., Andersen, K. R., Kilstrup, M., Martinussen, J., Switzer, R. L., & Willemoës, M. (2016) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00040-16 · Cited by 263 · see citing works
Morishita, T., Deguchi, Y., YAJIMA, M., Sakurai, T., & Yura, T. (1981) · Journal of Bacteriology · doi:10.1128/jb.148.1.64-71.1981 · Cited by 246 · see citing works
Bet-hedging during bacterial diauxic shift
Solopova, A., van Gestel, J., Weissing, F. J., Bachmann, H., Teusink, B., Kok, J., & Kuipers, O. P. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1320063111 · Cited by 245 · see citing works
Self-citationPhenotypic bistability in Escherichia coli's central carbon metabolism
Kotte, O., Volkmer, B., Radzikowski, J. L., & Heinemann, M. (2014) · Molecular Systems Biology · doi:10.15252/msb.20135022 · Cited by 242 · see citing works
Chance and necessity in the evolution of minimal metabolic networks
Pál, C., Papp, B., Lercher, M. J., Csermely, P., Oliver, S. G., & Hurst, L. D. (2006) · Nature · doi:10.1038/nature04568 · Cited by 239 · see citing works
Comparative Genomics of Enzymes in Flavor-Forming Pathways from Amino Acids in Lactic Acid Bacteria
Liu, M., Nauta, A., Francke, C., & Siezen, R. J. (2008) · Applied and Environmental Microbiology · doi:10.1128/aem.00150-08 · Cited by 230 · see citing works
Bosdriesz, E., Douwe Molenaar, B., Teusink, B., & Bruggeman, F. J. (2015) · FEBS Journal · doi:10.1111/febs.13258 · Cited by 229 · see citing works
Self-citationTrade-off Mechanisms Shaping the Diversity of Bacteria
Ferenci, T. (2015) · Trends in Microbiology · doi:10.1016/j.tim.2015.11.009 · Cited by 220 · see citing works
Multifactorial Diversity Sustains Microbial Community Stability
Erkus, O., de Jager, V. C. L., Spus, M., van Alen-Boerrigter, I. J., van Rijswijck, I. M. H., Hazelwood, L., Janssen, P. W. M., van Hijum, S. A. F. T., Kleerebezem, M., & Smid, E. J. (2013) · The ISME Journal · doi:10.1038/ismej.2013.108 · Cited by 217 · see citing works
Kinetics of growth and sugar consumption in yeasts
van Dijken, J. P., Weusthuis, R. A., & Pronk, J. T. (1993) · Antonie van Leeuwenhoek · doi:10.1007/bf00871229 · Cited by 216 · see citing works
Functioning of a metabolic flux sensor in <i>Escherichia coli</i>
Kochanowski, K., Volkmer, B., Gerosa, L., Haverkorn van Rijsewijk, B. R., Schmidt, A., & Heinemann, M. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1202582110 · Cited by 196 · see citing works
Chubukov, V., Uhr, M., Le Chat, L., Kleijn, R. J., Jules, M., Link, H., Aymerich, S., Stelling, J., & Sauer, U. (2013) · Molecular Systems Biology · doi:10.1038/msb.2013.66 · Cited by 191 · see citing works
Teusink, B., van Enckevort, F. H. J., Francke, C., Wiersma, A., Wegkamp, A., Smid, E. J., & Siezen, R. J. (2005) · Applied and Environmental Microbiology · doi:10.1128/aem.71.11.7253-7262.2005 · Cited by 180 · see citing works
Self-citationAvailability of public goods shapes the evolution of competing metabolic strategies
Bachmann, H., Fischlechner, M., Rabbers, I., Barfa, N., dos Santos, F. B., Douwe Molenaar, B., & Teusink, B. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1308523110 · Cited by 176 · see citing works
Self-citationRai, A. K., Sanjukta, S., & Jeyaram, K. (2015) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2015.1068736 · Cited by 146 · see citing works
Experimental Evolution of Metabolic Dependency in Bacteria
D’Souza, G. G., & Kost, C. (2016) · PLoS Genetics · doi:10.1371/journal.pgen.1006364 · Cited by 146 · see citing works
The Efficient Clade: Lactic Acid Bacteria for Industrial Chemical Production
Sauer, M., Rußmayer, H., Grabherr, R. M., Peterbauer, C., & Marx, H. (2017) · Trends in biotechnology · doi:10.1016/j.tibtech.2017.05.002 · Cited by 143 · see citing works
Is the Glycolytic Flux in Lactococcus lactisPrimarily Controlled by the Redox Charge?
Neves, A. R., Ventura, M. R., Mansour, N. M., Shearman, C. A., Gasson, M. J., Maycock, C. D., Ramos, A., & Santos, H. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m202573200 · Cited by 135 · see citing works
Systems Solutions by Lactic Acid Bacteria: From Paradigms to Practice
de Vos, W. M. (2011) · Microbial Cell Factories · doi:10.1186/1475-2859-10-s1-s2 · Cited by 134 · see citing works
Pastink, M. I., Teusink, B., Pascal Hols, A., Visser, S., de Vos, W. M., & Hugenholtz, J. (2009) · Applied and Environmental Microbiology · doi:10.1128/aem.00138-09 · Cited by 129 · see citing works
Self-citationOptimality and sub-optimality in a bacterial growth law
Towbin, B. D., Kohanim, Y. K., Bren, A., Doron, S., Sorek, R., & Alon, U. S. (2017) · Nature Communications · doi:10.1038/ncomms14123 · Cited by 129 · see citing works
Flahaut, N. A. L., Wiersma, A., van de Bunt, B., Martens, D. E., Schaap, P. J., Sijtsma, L., dos Santos, V. A. P. M., & de Vos, W. M. (2013) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-013-5140-2 · Cited by 128 · see citing works
Few regulatory metabolites coordinate expression of central metabolic genes in Escherichia coli
Kochanowski, K., Gerosa, L., Brunner, S. F., Christodoulou, D., Nikolaev, Y., & Sauer, U. (2017) · Molecular Systems Biology · doi:10.15252/msb.20167402 · Cited by 128 · see citing works
Kelleher, P., Bottacini, F., Mahony, J., Kilcawley, K. N., & van Sinderen, D. (2017) · BMC Genomics · doi:10.1186/s12864-017-3650-5 · Cited by 116 · see citing works
Constraint-based stoichiometric modelling from single organisms to microbial communities
Gottstein, W., Olivier, B. G., Bruggeman, F. J., & Teusink, B. (2016) · Journal of The Royal Society Interface · doi:10.1098/rsif.2016.0627 · Cited by 109 · see citing works
Self-citationHoek, M. J. A., & Merks, R. M. H. (2017) · BMC Systems Biology · doi:10.1186/s12918-017-0430-4 · Cited by 105 · see citing works
Understanding the physiology of Lactobacillus plantarum at zero growth
Goffin, P., van de Bunt, B., Giovane, M., Leveau, J. H. J., Höppener‐Ogawa, S., Teusink, B., & Hugenholtz, J. (2010) · Molecular Systems Biology · doi:10.1038/msb.2010.67 · Cited by 75 · see citing works
Self-citationRegulation of the Activity of Lactate Dehydrogenases from Four Lactic Acid Bacteria
Feldman‐Salit, A., Hering, S., Messiha, H. L., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.458265 · Cited by 71 · see citing works
Goel, A., Eckhardt, T. H., Puri, P., de Jong, A., dos Santos, F. B., Giera, M. A., Fusetti, F., de Vos, W. M., Kok, J., Poolman, B., et al. (2015) · Molecular Microbiology · doi:10.1111/mmi.13012 · Cited by 69 · see citing works
Self-citationKoebmann, B. J., Solem, C., Pedersen, M. B., Nilsson, D., & Jensen, P. R. (2002) · Applied and Environmental Microbiology · doi:10.1128/aem.68.9.4274-4282.2002 · Cited by 66 · see citing works
Phage-Host Interactions of Cheese-Making Lactic Acid Bacteria
Mahony, J., McDonnell, B., Casey, E., & van Sinderen, D. (2016) · Annual Review of Food Science and Technology · doi:10.1146/annurev-food-041715-033322 · Cited by 60 · see citing works
High local substrate availability stabilizes a cooperative trait
Bachmann, H., Douwe Molenaar, B., Kleerebezem, M., & Vlieg, J. E. T. V. H. (2010) · The ISME Journal · doi:10.1038/ismej.2010.179 · Cited by 58 · see citing works
Solis-Escalante, D., Kuijpers, N. G. A., Barrajón, N., van den Broek, M. A., Pronk, J. T., Daran, J.-M. G., & Daran-Lapujade, P. A. S. (2015) · Eukaryotic Cell · doi:10.1128/ec.00064-15 · Cited by 46 · see citing works
Veith, N., Solheim, M., van Grinsven, K. W. A., Olivier, B. G., Levering, J., Grosseholz, R., Hugenholtz, J., Holo, H., Nes, I., Teusink, B., et al. (2015) · Applied and Environmental Microbiology · doi:10.1128/aem.03279-14 · Cited by 42 · see citing works
Levering, J., Fiedler, T., Sieg, A., van Grinsven, K. W. A., Hering, S., Veith, N., Olivier, B. G., Klett, L. C., Hugenholtz, J., Teusink, B., et al. (2016) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2016.01.035 · Cited by 37 · see citing works
Self-citationvan Heerden, J. H., Bruggeman, F. J., & Teusink, B. (2014) · BioEssays · doi:10.1002/bies.201400108 · Cited by 34 · see citing works
Self-citationGroßeholz, R., Koh, C.-C., Veith, N., Fiedler, T., Strauß, M., Olivier, B. G., Collins, B. C., Schubert, O. T., Bergmann, F., Kreikemeyer, B., et al. (2016) · npj Systems Biology and Applications · doi:10.1038/npjsba.2016.17 · Cited by 33 · see citing works
Lactobacillus gasseri requires peptides, not proteins or free amino acids, for growth in milk
Arakawa, K., Matsunaga, K., Takihiro, S., et al. (2014) · Journal of Dairy Science · doi:10.3168/jds.2014-8860 · Cited by 28 · see citing works
Murabito, E., Verma, M., Bekker, M., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0106453 · Cited by 27 · see citing works
Tracing regulatory routes in metabolism using generalised supply-demand analysis
Christensen, C. D., Hofmeyr, J. S., & Rohwer, J. M. (2015) · BMC Systems Biology · doi:10.1186/s12918-015-0236-1 · Cited by 16 · see citing works
Dolatshahi, S., Fonseca, L. L., & Voit, E. O. (2015) · Molecular BioSystems · doi:10.1039/c5mb00726g · Cited by 14 · see citing works
Petersen, K. V., Liu, J., Chen, J., et al. (2017) · Biotechnology Journal · doi:10.1002/biot.201700171 · Cited by 12 · see citing works
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Proteome constraints reveal targets for improving microbial fitness in nutrient‐rich environments
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Microbiota of Cheese Ecosystems: A Perspective on Cheesemaking
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- Authors
- Teusink, B., & Molenaar, D.
- Affiliations
- TiFN (NL)
- Corresponding author
- Teusink, Bas
- ORCID
- Teusink, Bas
- Venue
- Current Opinion in Systems Biology
- Publisher
- Elsevier BV
- Published
- 2017-12
- Volume
- 6
- Pages
- 7-13
- ISSN
- 2452-3100 (ISSN-L)
- PMC
- PMC7489361
- OpenAlex
- W2738197621
- Cited by
- 95
- References
- 59
- Citations by year
- 2026: 10 · 2025: 6 · 2024: 14 · 2023: 9 · 2022: 13 · 2021: 12 · 2020: 15 · 2019: 9 · 2018: 6 · 2012: 1
- FWCI
- 0.89
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Current Opinion in Systems Biology (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- VU Research Portal (publishedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- STW (13858)
- TI Food and Nutrition project (16MF01)
- EraSysApp project SysMilk (NWO 832.14.001)
- ITN MicroWine (643031)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- lactic acid bacteria, systems biology, bacterial metabolism, food fermentation, dairy products, meat products, fishery products, plant fermentation, bacterial adaptation, metabolic evolution, comparative metabolism, gut microbiota
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