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. 2024 Feb 9;14(2):247.
doi: 10.3390/life14020247.

Microbial Pathway Thermodynamics: Stoichiometric Models Unveil Anabolic and Catabolic Processes

Affiliations

Microbial Pathway Thermodynamics: Stoichiometric Models Unveil Anabolic and Catabolic Processes

Oliver Ebenhöh et al. Life (Basel). .

Abstract

The biotechnological exploitation of microorganisms enables the use of metabolism for the production of economically valuable substances, such as drugs or food. It is, thus, unsurprising that the investigation of microbial metabolism and its regulation has been an active research field for many decades. As a result, several theories and techniques were developed that allow for the prediction of metabolic fluxes and yields as biotechnologically relevant output parameters. One important approach is to derive macrochemical equations that describe the overall metabolic conversion of an organism and basically treat microbial metabolism as a black box. The opposite approach is to include all known metabolic reactions of an organism to assemble a genome-scale metabolic model. Interestingly, both approaches are rather successful at characterizing and predicting the expected product yield. Over the years, macrochemical equations especially have been extensively characterized in terms of their thermodynamic properties. However, a common challenge when characterizing microbial metabolism by a single equation is to split this equation into two, describing the two modes of metabolism, anabolism and catabolism. Here, we present strategies to systematically identify separate equations for anabolism and catabolism. Based on metabolic models, we systematically identify all theoretically possible catabolic routes and determine their thermodynamic efficiency. We then show how anabolic routes can be derived, and we use these to approximate biomass yield. Finally, we challenge the view of metabolism as a linear energy converter, in which the free energy gradient of catabolism drives the anabolic reactions.

Keywords: elementary conversion modes; energy converter; energy metabolism; metabolic networks.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest.

Figures

Figure 1
Figure 1
The view of microbial metabolism as a thermodynamic energy converter. Catabolic reactions have a large negative free energy gradient, driving anabolic reactions [14].
Figure 2
Figure 2
Standard Gibbs free energies of all catabolic pathways, normalized to carbon mole. The catabolic pathways were derived using elementary conversion modes (ECMs) calculated from the E. coli core network. Red symbolizes ECMs that use oxygen, while blue denotes ECMs not using oxygen. Filled bars belong to ECMs that include no compounds with the element nitrogen, while empty ones include nitrogen-containing metabolites. The black crosses indicate the maximal yield of ATP per carbon mole nutrient for each ECM (right axis).
Figure 3
Figure 3
Thermodynamic characterization of catabolic routes in the S. cerevisiae genome-scale model (iND750) for α-ketoglutarate, glucose, xylose, and pyruvate as carbon sources. Additionally, oxygen is allowed to be a substrate in the calculation of the elementary conversion modes. The efficiency is based on a typical value of 46.5 kJ/mol for the production of ATP in E. coli [43]. For comparison we also calculated ATP production and efficiency based on data by [36]. Only ECMs are plotted with an ATP yield higher than 0.001 mol/C-mol.
Figure 4
Figure 4
The catabolic stoichiometric coefficients and thermodynamic driving forces determined for the chemostat growth of E. coli [36] and S. cerevisiae [37] at different dilution rates. All coefficients are given in mol/C-mol substrate, except for ethanol and acetate, which are given in C-mol/C-mol substrate. For E. coli, CO2 production is identical to O2 consumption. The thermodynamic driving force is given as the standard energy of reaction of the overall catabolic conversion, normalized to one carbon mole of substrate.
Figure 5
Figure 5
Metabolic fluxes as functions of the catabolic driving force. Shown are the catabolic (blue), anabolic (red), and total (green) glucose consumption rates in dependence of the catabolic driving force, ΔcatG. On the x-axis on the top, the force ratio x=ΔcatG/ΔanaG is given.
Figure 6
Figure 6
Catabolic and anabolic powers, as well as the power of ATP synthesis as a function of growth rate. Catabolic power is depicted in red, anabolic power in blue, and ATP synthase power in black. Circles present results for S. cerevisiae, crosses for E. coli.

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