earticle

영어

Extensive genetic modifications have been made to improve the performance of the bioreactor
systems. Although metabolic engineering has been paid much attention with some success in
practice, the pathway modifications based on the specific genes knockouts and/or amplifications
by plasmids do not necessarily lead to the significant improvement in the cell growth and/or the
specific metabolite production without profound insight into the metabolic regulation. Although
much information is available on genetic regulation, biochemistry, and physiology of cellular
metabolism, we are still far from understanding its overall regulation mechanism. It is strongly
desired that different levels of (omics) information be integrated by comparison of the data for
different mutants and/or the data obtained at different culture environments with the aid of
systems biology approach. Among the different levels of information, the metabolic flux
distribution is located on top of them, and it is quite important for understanding the whole cell
metabolism in practice. We have, so far, established the 13C-metabolic flux analysis method for
the continuous culture using NMR, GC-MS, and/further extended to the batch culture using CETOF/ MS. It was found that the cell metabolism significantly changes with respect to time for
specific gene knockout mutants as well as the wild type based on 13C-metabolic flux analysis.
We have also attempted to compare the flux data with other levels of information. We have also
investigated the effects of different carbon sources, nitrogen levels, phosphate levels,
temperature, and pH on the cell metabolism in view of global regulators and metabolic pathway
genes. Moreover, we are now developing a model which can simulate the metabolic changes
due to specific gene knockout. The goal of our research is to understand the whole cell
metabolism, and to realize its mechanism into the computer for the systematic cell design of
E.coli for the production of next generation bioenergy.