PATHWAY ANALYSIS OF OXYGEN UTILIZATION AND TRICARBOXYLIC-ACID CYCLE ACTIVITY IN SACCHAROMYCES-CEREVISIAE GROWING ON GLUCOSE

A method is proposed to quantitatively analyze the oxygen utilization of Saccharomyces cerevisiae growing on glucose through the three reduc ing-equivalent-generating routes, i.e., biomass synthesis, TCA cycle ( including glycolysis) and product formation. Calculations with literat ure data showed that, under conditions of purely oxidative and glucose -limited growth, the TCA cycle activity of S. cerevisiae accounts for over 70% and biosynthesis for 30% of the total oxygen consumption or l ess, independent of the assumed route for the generation of NADPH(2) r equired for biosynthesis. Under conditions of acetate production (but without ethanol formation) reduced NADH(2) formation via TCA cycle act ivity was calculated, indicating saturation or depression of the TCA c ycle activity. With the onset of ethanol production at high growth rat e, product formation can contribute up to 7-9% of the total oxygen con sumption and the contribution of biosynthesis appeared to decline. Mar kedly lower values (30-72%) for NADH(2) formation via TCA cycle were o btained for cultures under transition from glucose limitation to gluco se excess. It was found that the presence of glucose in cultures repre sses the activity of TCA cycle but not the respiratory capacity of S. cerevisiae. Under these conditions biosynthesis and product formation may contribute to the major portion of oxygen consumption. It was also found that the presence of high ethanol concentration in cultures obv iously inhibits the activity of the TCA cycle. From these calculations it can be concluded that bottlenecks in the oxidative glucose metabol ism of S. cerevisiae occur at the level of the TCA cycle or beyond. Th is is in accordance with recent experimental results.