Impact of nutrient excess on physiology and metabolism of Sulfolobus acidocaldarius

Overflow metabolism is a well-known phenomenon that describes the seemingly
wasteful and incomplete substrate oxidation by aerobic cells, such as yeasts,
bacteria, and mammalian cells, even when conditions allow for total combustion
via respiration. This cellular response, triggered by an excess of C-source, has not
yet been investigated in archaea. In this study, we conducted chemostat cultivations
to compare the metabolic and physiological states of the thermoacidophilic
archaeon Sulfolobus acidocaldarius under three conditions, each with gradually
increasing nutrient stress. Our results show that S. acidocaldarius has different
capacities for the uptake of the two C-sources, monosodium glutamate and glucose.
A saturated tricarboxylic acid cycle at elevated nutrient concentrations affects
the cell’s ability to deplete its intermediates. This includes deploying additional
cataplerotic pathways and the secretion of amino acids, notably valine, glycine,
and alanine, while glucose is increasingly metabolized via glycogenesis. We did
not observe the secretion of common fermentation products, like organic acids.
Transcriptomic analysis indicated an upregulation of genes involved in fatty acid
metabolism, suggesting the intracellular conservation of energy. Adapting respiratory
enzymes under nutrient stress indicated high metabolic flexibility and robust
regulatory mechanisms in this archaeon. This study enhances our fundamental
understanding of the metabolism of S. acidocaldarius.