Toward systematic metabolic engineering based on the analysis of metabolic regulation by the integration of different levels of information

An integrated analysis of enzyme activities, cofactor pools and metabolic fluxes in baculovirus-infected Spodoptera frugiperda Sf9 cells

“…The combined analysis of different levels of metabolism regulation (gene transcription, proteome, enzyme activities, metabolome and fluxome) has been successfully applied to characterize and improve microbial processes (Bernal et al, 2007;Shimizu, 2009). However, the application of these methodologies to animal cellbased bioprocesses has been much less, especially in the case of insect cells.…”

Brief overview of metabolic regulation of a bacterial cell

“…A better understanding of gene and protein expressions for cells under physiological changes is of primary importance. The most important notion is to regard the cell as a whole in its entirety in relation to global metabolic regulation, rather than through individual reactions (Shimizu, 2004;2009). In this chapter, metabolic regulation of a bacterial cell such as E. coli , in response to different carbon sources and lower oxygen concentrations, is explained based on protein expressions, etc.…”

Engineering

“…Moreover, the effects of targeted strain modifications are typically underestimated, since they do not always result in significant differences in cell growth or production of specific metabolites. Combination of techniques such as genomics, transcriptomics, proteomics, metabolomics and fluxomics can unravel the particular cellular state during a defined condition by providing snapshots of different levels of metabolism [111]. However, in order to turn this information into knowledge of new potential engineering targets, adequate comparisons must be established.…”

“…Other works have also characterized the global transcriptional response to the presence of high levels of L-PHE or SHK in simple and complex media [120,121] or starvation conditions [122], revealing metabolic information that can be used for further improvement of the strains and cultivation conditions. Along with data obtained by high-throughput systems, modeling of metabolism by mathematical approaches has become an important tool for analyzing cell responses and unravel the metabolic regulation between the cell information/control systems [111]. Moreover, genome-scale models of metabolism have been analyzed by constraint-based approaches [123].…”