Identification and control of oxidative metabolism in Saccharomyces cerevisiae during transient growth using calorimetric measurements

The objective of this study was to characterize the dynamic adaptation of the oxidative capacity of Saccharomyces cerevisiae to an increase in the glucose supply rate and its implications for the control of a continuous culture designed to produce biomass without allowing glucose to be diverted into the reductive metab. Continuous cultures subjected to a sudden shift-up in the diln. rate showed that the glucose uptake rate increased immediately to the new feeding rate but that the oxygen consumption could not follow fast enough to ensure a completely oxidative metab. Thus, part of the glucose assimilated was degraded by the reductive metab., resulting in a temporary decrease of biomass concn., even if the final diln. rate was below Dcrit. The dynamic increase of the specific oxygen consumption rate, qo2, was characterized by an initial immediate jump followed by a first-order increase to the max. value. It could be modeled using three parameters denoted qo2jump, qo2max, and a time const. t. The values for the first two of the parameters varied considerably from one shift to another, even when they were performed under identical conditions. On the basis of this model, a time-dependent feed flow rate function was derived that should permit an increase in the diln. rate from one value to another without provoking the appearance of reductive metab. The idea was to increase the glucose supply in parallel with the dynamic increase of the oxidative capacity of the culture, so that all of the assimilated glucose could always be oxidized. Nevertheless, corresponding feed-profile expts. showed that deviations in the reductive metab. could not be completely suppressed due to variability in the model parameters. Therefore, a proportional feedback controller using heat evolution rate measurements was implemented. Calorimetry provides an excellent and rapid est. of the metabolic activity. Satisfactory control was achieved and led to const. biomass yields. Ethanol accumulated only up to 0.49 g L-1 as compared to an accumulation of 1.82 g L-1 without online control in the shift-up expt. to the same final diln. rate. [on SciFinder (R)]