Modeling and simulation of the redox regulation of the metabolism in at different oxygen concentrations.

BACKGROUND

Microbial production of biofuels and biochemicals from renewable feedstocks has received considerable recent attention from environmental protection and energy production perspectives. Many biofuels and biochemicals are produced by fermentation under oxygen-limited conditions following initiation of aerobic cultivation to enhance the cell growth rate. Thus, it is of significant interest to investigate the effect of dissolved oxygen concentration on redox regulation in , a particularly popular cellular factory due to its high growth rate and well-characterized physiology. For this, the systems biology approach such as modeling is powerful for the analysis of the metabolism and for the design of microbial cellular factories.

RESULTS

Here, we developed a kinetic model that describes the dynamics of fermentation by taking into account transcription factors such as ArcA/B and Fnr, respiratory chain reactions and fermentative pathways, and catabolite regulation. The hallmark of the kinetic model is its ability to predict the dynamics of metabolism at different dissolved oxygen levels and facilitate the rational design of cultivation methods. The kinetic model was verified based on the experimental data for a wild-type strain. The model reasonably predicted the metabolic characteristics and molecular mechanisms of and gene-knockout mutants. Moreover, an aerobic-microaerobic dual-phase cultivation method for lactate production in a -knockout mutant exhibited promising yield and productivity.

CONCLUSIONS

It is quite important to understand metabolic regulation mechanisms from both scientific and engineering points of view. In particular, redox regulation in response to oxygen limitation is critically important in the practical production of biofuel and biochemical compounds. The developed model can thus be used as a platform for designing microbial factories to produce a variety of biofuels and biochemicals.