Modeling of metabolic regulation in bacterial continuous cultures

Shiv Baloo, Purdue University

Abstract

Mathematical models for microbial growth based on reaction kinetics are generally successful in predicting the behavior of batch and steady state continuous cultures. In striking contrast, these models fail in predicting transient continuous culture behavior primarily because they neglect the pronounced role of metabolic regulation under these circumstances. This work exploits general cybernetic ideas advanced previously (Kompala et al., 1984) to develop a model that significantly overcomes the foregoing deficiencies. The basis of the model is the cybernetic framework with its simple representation of the net outcome of metabolic regulation in the form of cybernetic (control) variables calculated from optimal objectives. The development of the model explicitly accounts for the 'lumped' internal resource which is optimally allocated towards the synthesis of key enzymes catalyzing the different cellular processes. The model also includes a description of the increased maintenance demand observed at very low growth rates. The regulation arising from competition between growth and maintenance processes for the limited amounts of substrate and internal resource available at low growth rates is represented by cybernetic variables. The single substrate model is extended to describe microbial growth on multiple substitutable substrates. The additional regulation due to the presence of multiple substrates in the environment is represented solely by the cybernetic variables; thus the model complexity is not increased. Furthermore, since single substrate parameters characterize the substrate and the organism, no new constants are introduced in the mixed substrate model. The steady-state growth of Klebsiella pneumoniae on glucose and xylose showed simultaneous utilization of both substrates at the low growth rates and a preferential utilization of glucose at the high growth rates. Metabolic regulation also controlled the behavior of the culture following changes in the dilution rate and a switch in the growth-limiting nutrient from glucose to xylose as well as in the mixed substrate batch experiments. The mixed substrate model described all the experimental results using the same parameters identified from single substrate experiments with the singular exception of the constitutive rate of enzyme synthesis. It is possible that the history of the cell could affect this parameter.

Degree

Ph.D.

Advisors

Ramkrishna, Purdue University.

Subject Area

Chemical engineering

COinS