Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Are Microbes Thermodynamically Optimised Self-Reproducing Machines?

Version 1 : Received: 17 December 2019 / Approved: 19 December 2019 / Online: 19 December 2019 (07:00:02 CET)

How to cite: Saadat, N.P.; Nies, T.; Rousset, Y.; Ebenhöh, O. Are Microbes Thermodynamically Optimised Self-Reproducing Machines?. Preprints 2019, 2019120245. Saadat, N.P.; Nies, T.; Rousset, Y.; Ebenhöh, O. Are Microbes Thermodynamically Optimised Self-Reproducing Machines?. Preprints 2019, 2019120245.


To understand microbial growth with mathematical models has a long tradition that dates back to the pioneering work of Jacques Monod in the 1940s. Growth laws are simple mathematical expressions that aim at describing growth rates of microbes as functions of external parameters, in particular nutrient concentrations. These laws are now widely applied to construct, e.g., dynamic ecosystem models. However, to explain the growth laws from underlying (first) principles is extremely challenging. In the second half of the 20th century, numerous experimental approaches aimed at precisely measuring heat production during microbial growth to determine the entropy balance in a growing cell and to quantify the exported entropy. This has led to the development of thermodynamic theories of microbial growth, which have generated fundamental understanding and identified principle limitations of the growth process. Whereas these approaches considered a growing microbe as a black box, modern theories heavily rely on genomic resources to describe and model genome-scale networks to explain microbial growth. Interestingly, however, thermodynamic constraints are often included in modern modelling approaches only in a rather superficial fashion, and it appears that recent modelling approaches and classical theories are disconnected fields. In order to stimulate a closer interaction between these fields, we here review various theoretical approaches that aim at describing microbial growth based on thermodynamic principles. We start with classical black-box models of cellular growth, and continue with genome-scale modelling approaches that include thermodynamics, before we place these models in the context of fundamental considerations based on non-equilibrium statistical mechanics. We conclude by identifying conceptual overlaps between the fields and suggest how the various types of theories and models can be integrated. We outline how concepts from one approach may help to inform or constrain another, and we demonstrate how genome-scale models can be used to infer classical black-box parameters, which are experimentally accessible in growth experiments. Such integration will allow understanding to what extent microbes can be viewed as thermodynamic machines, and how close they operate to theoretical optima.


energy; entropy; anabolism;catabolism; microbial cultures; biotechnology


Biology and Life Sciences, Biophysics

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