Industrial & Engineering Chemistry Research, Vol.49, No.20, 9738-9752, 2010
Selection of Best Indicators for Ranking and Determination of Bottleneck Enzymes in Metabolic Reaction Systems
Dynamic logarithmic gain and its modifications can be theoretically used as a bottleneck ranking (BR) indicator in a metabolic reaction system. However, it is not sufficiently explicit whether they can be successfully used in practical applications. The present work therefore focuses on the selection of best BR indicators in both instantaneous and overall cases. A modified ethanol fermentation model is used as a case study. The results indicate that the mathematical product of dynamic logarithmic gain and desired product concentration at a given time is the best instantaneous BR indicator, whereas its value at the end time of the fermentation process is the best overall BR indicator. The former is useful for observing the time course of the desired product concentration and determining a process time to be terminated. The latter is for ranking bottleneck enzymes to determine which enzyme activity should be changed to attain a higher desired product concentration. Moreover, discussion is made on the utilization of the overall BR indicators to predict how much the final desired product concentration is increased.