The structured cybernetic model recently formulated by Ramkrishna's group provides a rigorous modeling framework for describing dynamic regulatory processes by the microorganisms (Young, 2005; Young and Ramkrishna, 2007). This model can address various metabolic engineering issues including the effects of gene knockouts, targeted overexpression and attenuation of genes. Meanwhile, a hybrid modeling concept has been introduced as an interesting alternative to Young's framework due to its simpler computational structure and tested for E. coli (Kim, 2005). Formulation of hybrid models requires two stages: first, elementary flux modes (or convex basis vectors) are extracted from convex analysis of flux-balance equations and then, cybernetic control laws determine the substrate uptake pattern taking each elementary mode as a basic reaction unit. It is possible to regard the hybrid model as a simplified version of Young's framework from the fact that the latter readily reduces to the former on assuming pseudo steady-state for internal metabolites.

In this study, the application of the hybrid model is extended to the recombinant S. cerevisiae fermenting glucose and xylose. For the case of recombinant yeasts with complex metabolic network structure, hybrid modeling would become inefficient due to the increased number of elementary modes. A rational methodology is thus developed to select a minimum subset of elementary modes without sacrificing simulation accuracy, by which computational efficiency as a merit of hybrid modeling is conserved. It is shown that the diauxic behavior of recombinant yeasts is efficiently described by the hybrid model following this strategy. Besides, some efforts are being made to see the possibility whether the hybrid model can also be used as a tool for metabolic engineering applications as Young's model.

References

Kim, J. I. (2005) A Hybrid Model of Anaerobic E. coli: Cybernetic Approach and Elementary Mode Analysis. MS Dissertation, Purdue University

Young, J. D. (2005) A System-Level Mathematical Description of Metabolic Regulation Combining Aspects of Elementary Mode Analysis with Cybernetic Control Laws. PhD Dissertation, Purdue University

Young, J. D., Ramkrishna, D. (2007) On the Matching and Proportional Laws of Cybernetic Models. Biotechnology Progress 23, 83-99