The application of thermodynamics to microbial growth has a long tradition that originated in the middle of the 20th century. This approach reflects the view that self-replication is a thermodynamic process that is not fundamentally different from mechanical thermodynamics. The key distinction is that a free energy gradient is not converted into mechanical (or any other form of) energy but rather into new biomass. As such, microbes can be viewed as energy converters that convert a part of the energy contained in environmental nutrients into chemical energy that drives self-replication. Before the advent of high-throughput sequencing technologies, only the most central metabolic pathways were known. However, precise measurement techniques allowed for the quantification of exchanged extracellular nutrients and heat of growing microbes with their environment. These data, together with the absence of knowledge of metabolic details, drove the development of so-called black-box models, which only consider the observable interactions of a cell with its environment and neglect all details of how exactly inputs are converted into outputs. Now, genome sequencing and genome-scale metabolic models (GEMs) provide us with unprecedented detail about metabolic processes inside the cell. However, mostly due to computational complexity issues, the derived modelling approaches make surprisingly little use of thermodynamic concepts. Here, we review classical black-box models and modern approaches that integrate thermodynamics into GEMs. We also illustrate how the description of microbial growth as an energy converter can help to understand and quantify the trade-off between microbial growth rate and yield.
Keywords: black box models; efficiency; genome-scale metabolic models; thermodynamics.
© 2021 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.