title: Catabolite regulation analysis of Escherichia coli for acetate overflow mechanism and co-consumption of multiple sugars based on systems biology approach using computer simulation.
abstract: It is quite important to understand the basic principle embedded in the main metabolism for the interpretation of the fermentation data. For this, it may be useful to understand the regulation mechanism based on systems biology approach. In the present study, we considered the perturbation analysis together with computer simulation based on the models which include the effects of global regulators on the pathway activation for the main metabolism of Escherichia coli. Main focus is the acetate overflow metabolism and the co-fermentation of multiple carbon sources. The perturbation analysis was first made to understand the nature of the feed-forward loop formed by the activation of Pyk by FDP (F1,6BP), and the feed-back loop formed by the inhibition of Pfk by PEP in the glycolysis. Those together with the effect of transcription factor Cra caused by FDP level affected the glycolysis activity. The PTS (phosphotransferase system) acts as the feed-back system by repressing the glucose uptake rate for the increase in the glucose uptake rate. It was also shown that the increased PTS flux (or glucose consumption rate) causes PEP/PYR ratio to be decreased, and EIIA-P, Cya, cAMP-Crp decreased, where cAMP-Crp in turn repressed TCA cycle and more acetate is formed. This was further verified by the detailed computer simulation. In the case of multiple carbon sources such as glucose and xylose, it was shown that the sequential utilization of carbon sources was observed for wild type, while the co-consumption of multiple carbon sources with slow consumption rates were observed for the ptsG mutant by computer simulation, and this was verified by experiments. Moreover, the effect of a specific gene knockout such as Δpyk on the metabolic characteristics was also investigated based on the computer simulation.
authors.affiliation: Department of Bioscience and Bioinformatics, Kyushu Institute of Technology, Iizuka, Fukuoka 820-8502, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Matsuoka
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Shimizu
mesh_terms: D000085:Acetates / Q000378:metabolism*; D057465:Catabolite Repression; D002952:Citric Acid Cycle; D003198:Computer Simulation; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D025461:Feedback, Physiological; D005285:Fermentation; D005635:Fructosediphosphates / Q000378:metabolism; D055786:Gene Knockout Techniques; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis; D008954:Models, Biological; D010427:Pentose Phosphate Pathway; D010728:Phosphoenolpyruvate / Q000378:metabolism; D010770:Phosphotransferases / Q000235:genetics / Q000378:metabolism; D011770:Pyruvate Kinase / Q000235:genetics / Q000378:metabolism; D049490:Systems Biology / Q000379:methods*; D014994:Xylose / Q000378:metabolism*
chemical_list: D000085:Acetates; D005635:Fructosediphosphates; D010728:Phosphoenolpyruvate; D014994:Xylose; D010770:Phosphotransferases; D011770:Pyruvate Kinase; D005947:Glucose; C029063:fructose-1,6-diphosphate
keywords: 6-phosphogluconate; 6-phosphogluconate dehydrogenase; 6PG; Ack; Acs; CCR; CIT; CS; Catabolite regulation; Computer simulation; Cya; E4P; EI; EII; Eno; Escherichia coli; F6P; FDP; Fbp; G6P; G6PDH; GAP; GF6P; GLC; GOX; Glk; HPr; ICDH; ICI; Icl; MAL; MDH; MS; Mez; Modeling; Multiple carbon sources; OAA; PDH; PEP; PGDH; PP pathway; PTS; PYR; Pck; Pfk; Ppc; Pps; Pta; Pyk; R5P; RU5P; Rpe; Rpi; S7P; SUC; Systems biology; TCA cycle; TP; Tal; TktA; TktB; X5P; XT; XYL; XYLU; Xyi; Xyk; acetate kinase; acetyl coenzyme A synthetase; adenylate cyclase; carbon catabolite repression; citrate; citrate synthase; enolase; enzyme I; enzyme II; erythrose-4-phosphate; fructose bisphosphatase; fructose-1.6-bisphosphate; fructose-6-phosphate; glucokinase; glucose; glucose-6-phosphate; glucose-6-phosphate and fructose-6-phosphate; glucose-6-phosphate dehydrogenase; glycelaldehyde-3-phosphate; glyoxylate; histidine-phosphorylatable protein; isocitrate; isocitrate dehydrogenase; isocitrate lyase; malate; malate dehydrogenase; malate synthase; malic enzyme; oxaloacetate; pentose phosphate pathway; phosphoenol pyruvate; phosphoenolpyruvate carboxykinase; phosphoenolpyruvate carboxylase; phosphoenolpyruvate synthase; phosphofructokinase; phosphotransacetylase; phosphotransferase system; pyruvate; pyruvate dehydrogenase; pyruvate kinase; ribose phosphate isomerase; ribose-5-phosphate; ribulose phosphate epimerase; ribulose-5-phosphate; sedoheptulose-7-phosphate; succinate; transaldolase; transketolase I; transketolase II; tricarboxylic acid cycle; triose phosphate; xylose; xylose isomerase; xylose transport; xylulokinase; xylulose; xylulose-5-phosphate; α-ketoglutarate; αKG