Theoretical analysis of amino acid-producing Escherichia coli using a stoichiometric model and multivariate linear regression.
This work demonstrates a novel computational approach combining flux balance modeling with statistical methods to identify correlations among fluxes in a metabolic network, providing insight as to how the fluxes should be redirected to achieve maximum product yield. The procedure is demonstrated using the example of amino acid production from an industrial Escherichia coli production strain and a hypothetical engineered strain overexpressing two heterologous genes. Regression analysis based on a random sampling of 5,000 points within the feasible solution space of the E. coli stoichiometric network suggested that increased activity of the glyoxylate cycle or PEP carboxylase and elimination of malic enzyme will improve lysine and arginine synthesis.
Van Dien
Stephen J
SJ
Functional Genomics Group, Institute of Life Sciences, Ajinomoto Co., Inc., Kawasaki 210-8681, Japan. svandien@genomatica.com
Iwatani
Shintaro
S
Usuda
Yoshihiro
Y
Matsui
Kazuhiko
K
D000596:Amino Acids / Q000096:biosynthesis* / Q000235:genetics; D003198:Computer Simulation; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D016014:Linear Models; D008954:Models, Biological; D015233:Models, Statistical; D015999:Multivariate Analysis; D025341:Principal Component Analysis; D015202:Protein Engineering / Q000379:methods*; D011994:Recombinant Proteins / Q000378:metabolism*; D012044:Regression Analysis
D000596:Amino Acids; D029968:Escherichia coli Proteins; D011994:Recombinant Proteins