Strain improvement by metabolic engineering: lysine production as a case study for systems biology.
A central goal of systems biology is the elucidation of cell function and physiology through the integrated use of broad based genomic and physiological data. Such systemic approaches have been employed extensively in the past, as they are a central element of metabolic flux analysis, the distribution of kinetic control in pathways, and the key differentiating characteristic of metabolic engineering. In one case study, these tools have been applied to the improvement of lysine-producing strains of Corynebacterium glutamicum. The systematic study of the physiology of this organism allowed the identification of specific metabolic targets and subsequently led to significant improvements in product yield and productivity. This case study can serve as a guide for the development of systems biology tools for the utilization of large volumes of cell- and genome-wide transcriptional and physiological data.
Koffas
Mattheos
M
Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, 904 Furnas Hall, Buffalo, New York 14260, USA. mkoffas@eng.buffalo.edu
Stephanopoulos
Gregory
G
D048230:Corynebacterium glutamicum / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D016680:Genome, Bacterial; D018698:Glutamic Acid / Q000378:metabolism; D007553:Isotope Labeling / Q000379:methods; D008239:Lysine / Q000096:biosynthesis*; D049490:Systems Biology
D018698:Glutamic Acid; D008239:Lysine