Abstract
It becomes more and more important to develop appropriate models for the efficient design of the cell factory for microbial biofuels and biochemical productions, since the appropriate model can predict the effect of culture environment and/or the specific pathway genes knockout on the growth characteristics. Among various modeling approaches, kinetic modeling is promising in the sense of realizing the essential feature of metabolic regulation. A brief overview is given for the current status of the kinetic modeling of the cell metabolism from the point of view of metabolic regulation focusing on Escherichia coli (but not limited to E. coli). For the proper modeling, it is important to realize the systems behavior by integrating different levels of information to understand and unravel the underlying principles of the living organisms, namely, it is important to properly understand how the environmental stimuli are detected by the cell, how those are transduced, and how the cell metabolism is regulated, and to express these into the model. In particular, it is important to incorporate the enzymatic regulations of Pyk, Pfk, and Ppc by fructose-1,6-bisphosphate (FBP), phosphoenol pyruvate (PEP), and acetyl-coenzyme A (AcCoA) to realize the flux-sensing and homeostatic behavior. The proper modeling for phosphotransferase system (PTS) and the transcriptional regulation by cAMP-Crp and Cra is also important to simulate the main metabolism in relation to catabolite regulation. The coordinated regulation between catabolic and anabolic (nitrogen source-assimilation) metabolisms may be simulated by the behavior of keto acid such as α-ketoglutarate (αKG). The metabolism under micro-aerobic conditions may be made by incorporating the global regulators such as ArcA/B and Fnr. It is quite important to develop quantitative kinetic models, which incorporate enzyme level and gene level regulations from the biological science and metabolic engineering points of view.
Highlights
Microbial production of biofuels and biochemicals from renewable resources or biomass has been paid recent attention from global sustainability and environmental protection points of view, and many attempts have been made for the cell design by metabolic engineering approach
The ultimate goal of systems biology is to reconstruct a cell system into the computer which can predict observable phenotypes. If this could be attained, the effects of culture environment and/ or the specific genetic mutation on the metabolism can be Matsuoka and Shimizu Bioresources and Bioprocessing (2015) 2:4 predicted without conducting many exhaustive experiments, and metabolic engineering may be made more efficient with verification by the experiment for the selected mutants in the optimized condition based on the computer simulation
The appropriate model can contribute for the efficient design of cell factories from the practical application point of view
Summary
Microbial production of biofuels and biochemicals from renewable resources or biomass has been paid recent attention from global sustainability and environmental protection points of view, and many attempts have been made for the cell design by metabolic engineering approach.
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