Dynamic modeling reveals a three-step response of Saccharomyces cerevisiae to high CO2 levels accompanied by increasing ATP demands.
Saccharomyces cerevisiae is often applied in large-scale bioreactors where gradients of dissolved CO2 exist. Under high CO2 pressure, the dissolved gas enters the microbe, causing multifold intracellular responses such as decrease of pH, increase of HCO3- and changes of ion balance. Effects of varying CO2 concentrations are multifold, hard to scale and hardly investigated. Hence, the multi-level response to CO2 shifts was summarized in a predicting ODE model with mass action kinetics, balancing electrochemical charges in steady-state growth conditions. Compared to experimental observations, the simulated dynamics of ion concentrations were found to be consistent. During CO2 shifts, the model predicts the initial depolarization of the membrane potential, the temporal pH drop and the activation of countermeasures such as Pma1-mediated H+ export and Trk1,2-mediated K+ import. In conclusion, extracellular cation concentrations and the cellular pH regulation are critical factors that determine physiology and cellular energy management. Consequently, pressure-induced CO2 gradients cause peaks of ATP demand which may occur in cells circulating in large-scale industrial bioreactors.
Gerhard
G
Eigenstetter
Ralf
R
Takors
D000222:Adaptation, Physiological; D000255:Adenosine Triphosphate / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D002245:Carbon Dioxide / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008564:Membrane Potentials / Q000187:drug effects; D011188:Potassium / Q000378:metabolism; D006180:Proton-Translocating ATPases / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism
D027682:Cation Transport Proteins; D029701:Saccharomyces cerevisiae Proteins; C085258:TRK2 protein, S cerevisiae; C068664:TRK1 protein, S cerevisiae; D002245:Carbon Dioxide; D000255:Adenosine Triphosphate; C092477:PMA1 protein, S cerevisiae; D006180:Proton-Translocating ATPases; D011188:Potassium
ATP; CO2 signal; HCO3−; ion balance; membrane potential; pH