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

Recent metabolic engineering were reviewed for the production of useful metabolites. Although much attention has been paid to metabolic engineering with some practical success, without profound insight into metabolic regulation, the modi. cation of pathways based on the knockout of corresponding genes and/or amplification by plasmids does not necessarily lead to a significant improvement in cell growth and/or the production of specific metabolites. Although much information is available on the genetic regulation, biochemistry, and physiology of cellular metabolism, we are still far from understanding their overall regulation. Metabolic flux distribution is the manifestation of regulation at the enzyme level of the concentrations of intracellular metabolites. Moreover, proteins ( including enzymes) are encoded by the corresponding metabolic pathway genes, which are under control of global regulators that respond to the environment. It is strongly desired that different levels of (omics) information be integrated by comparison of the data from different mutants and/or the different cultural environments using a systems biology approach. In particular, the roles of global regulators are quite important for metabolic regulation. (C) 2009 Elsevier B. V. All rights reserved.