Searching for principles of microbial physiology

Research output: Contribution to JournalArticleAcademicpeer-review


Why do evolutionarily distinct microorganisms display similar physiological behaviours? Why are transitions from high-ATP yield to low(er)-ATP yield metabolisms so widespread across species? Why is fast growth generally accompanied with low stress tolerance? Do these regularities occur because most microbial species are subject to the same selective pressures and physicochemical constraints? If so, a broadly-applicable theory might be developed that predicts common microbiological behaviours. Microbial systems biologists have been working out the contours of this theory for the last two decades, guided by experimental data. At its foundations lie basic principles from evolutionary biology, enzyme biochemistry, metabolism, cell composition and steady-state growth. The theory makes predictions about fitness costs and benefits of protein expression, physicochemical constraints on cell growth and characteristics of optimal metabolisms that maximise growth rate. Comparisons of the theory with experimental data indicates that microorganisms often aim for maximisation of growth rate, also in the presence of stresses; they often express optimal metabolisms and metabolic proteins at optimal concentrations. This review explains the current status of the theory for microbiologists; its roots, predictions, experimental evidence and future directions.

Original languageEnglish
Pages (from-to)821-844
Number of pages24
JournalFEMS Microbiology Reviews
Issue number6
Early online date21 Sept 2020
Publication statusPublished - 24 Nov 2020


FJB acknowledges funding from NWO-VIDI Grant 864.11.011 and BT from NWO-VICI Grant 865.14.005. We thank the following researchers for their contributions and discussions: Jan Berkhout, Evert Bosdriesz, Daan de Groot, Johan van Heerden, Matthias Heinemann, Joost Hulshof, Terry Hwa, Hidde de Jong, Stefan Klumpp, Wolfram Liebermeister, Timo Maarleveld, Steffen Klamt, Stefan Müller, Erik van Nimwegen, Elad Noor, Niclas Nordholt, Gosse Overal, Han Peters, Jack Pronk, Iraes Rabbers, Matt Scott, Peter Swain, Pieter Rein ten Wolde and Meike Wortel.

FundersFunder number
Nederlandse Organisatie voor Wetenschappelijk Onderzoek


    • biophysics
    • constrained biosynthetic resource allocation
    • evolutionary biology
    • mathematical modelling
    • microbial physiology
    • systems biology


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