Abstract
Redox metabolism plays an essential role in the central metabolic network of all living cells, connecting, but at the same time separating, catabolic and anabolic pathways. Redox metabolism is inherently linked to the excretion of overflow metabolites. Overflow metabolism allows for higher substrate uptake rates, potentially outcompeting other microorganisms for the same substrate. Within dynamically changing environments, overflow metabolism can act as storage mechanism, as is shown in many recently described processes. However, for complete understanding of these mechanisms, the intracellular state of the metabolism must be elucidated. In recent years, progress has been made in the field of metabolomics to improve the accuracy and precision of measurements of intracellular and intercompartmental metabolites. This article highlights several of these recent advances, with focus on redox cofactor measurements, both fluorescence and mass spectrometry based.
Highlights
The redox metabolism is commonly studied and interpreted under steady state conditions, where the transfer of electrons and metabolites inside the cell is balanced
The transfer of electrons between different reactions of the metabolic network is facilitated by electron carriers such as NADH, NADPH, FADH2, quinones and ferredoxins
NADPH is the cofactor used for anabolism like amino acid and lipid synthesis [1]
Summary
The redox metabolism is commonly studied and interpreted under steady state conditions, where the transfer of electrons and metabolites inside the cell is balanced. The achieved accumulation of PHB from extracellular acetate serves as carbon and electron source during the aerobic phase, both for biomass synthesis as well as refuelling of the intracellular glycogen and polyphosphate pools [5,23] These examples (see Table 1) show that dynamic balancing of electron sinks (and sources), including intracellular storage as well as overflow products, facilitate the maximization of substrate uptake rates, potentially generating a competitive advantage. Such a redox coupling can be used to link biomass synthesis with the product pathway This strategy can especially be exploited for products that generate a surplus of ATP (often referred to as catabolic products) and several approaches can be used [32]: (1) changing the cofactor specificity of either the product pathway or the catabolic pathway [33–35], (2) utilizing transhydrogenases to interconvert different electron carriers [36], (3) enforcing (electron and carbon) flux to the product by eliminating other electron sinks (like by-product pathways to glycerol or ethanol, and respiration) [37], (4) providing external secondary sources of electrons, such as formate, to increase intracellular reducing power [38].
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