Mathematical Modeling and Optimization of Cellulase Protein Production Using Trichoderma reesei RL-P37

Arun Tholudur, W. Fred Ramirez, James D. McMillan

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44 Scopus Citations


The enzyme cellulase, a multienzyme complex made up of several proteins, catalyzes the conversion of cellulose to glucose in an enzymatic hydrolysis- based biomass-to-ethanol process. Production of cellulase enzyme proteins in large quantities using the fungus Trichoderma reesei requires understanding the dynamics of growth and enzyme production. The method of neural network parameter function modeling, which combines the approximation capabilities of neural networks with fundamental process knowledge, is utilized to develop a mathematical model of this dynamic system. In addition, kinetic models are also developed. Laboratory data from bench-scale fermentations involving growth and protein production by T. reesei on lactose and xylose are used to estimate the parameters in these models. The relative performances of the various models and the results of optimizing these models on two different performance measures are presented. An approximately 33% lower root-mean- squared error (RMSE) in protein predictions and about 40% lower total RMSE is obtained with the neural network-based model as opposed to kinetic models. Using the neural network-based model, the RMSE in predicting optimal conditions for two performance indices, is about 67% and 40% lower, respectively, when compared with the kinetic models. Thus, both model predictions and optimization results from the neural network-based model are found to be closer to the experimental data than the kinetic models developed in this work. It is shown that the neural network parameter function modeling method can be useful as a 'macromodeling' technique to rapidly develop dynamic models of a process.

Original languageAmerican English
Pages (from-to)1-16
Number of pages16
JournalBiotechnology and Bioengineering
Issue number1
StatePublished - 1999

NREL Publication Number

  • NREL/JA-580-25515


  • Cellulase production
  • Kinetic modeling
  • Neural networks
  • Parameter function modeling
  • Trichoderma reesei


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