The Flux Control Analysis Of GTP Synthesizing Pathway In Bacillus.subtilis

Metabolic Control Analysis (MCA) is a quantitative analysis theory and an experimental methodology with the systemic view for metabolic regulation and control. Flux control analysis was carried out for the pathways around key metabolite branch point and the linear pathway: IMP-XMP-GMP-GDP-GTP in Bacillus.subtilis using top-down approach, Linlog kinetic models and transient metabolite concentrations approach. The analysis could be used as a guide to identify targets for metabolic engineering aiming at GTP synthesizing.In Bacillus.subtilis RH33, there are three branches around glucose-6-phosphate : the synthetic pathway of glucose-6-phosphate J1 , the PP pathway J2 and the pathway of Pyr-synthesizing. The flux control coefficients on the synthetic pathway of ribose-5-phosphate are C31=-0.539,C32=0.023,C33=1.516.For another branch point, the flux control coefficients on the GTP-synthesizing pathway are C31=0.125,C32=0.112,C33=0.763. The total GTP-synthesizing flux is represented by itself, so the flux control of the third pathway should be taken in order to mine the significant effect of control distribution in the way.In the linear pathway IMP-XMP-GMP-GTP, the flux control of GTP-synthesizing is distributed over enzymes of the pathway: C1=0.257,C2=0.315,C3=0.321,C4=0.107. The FCCs of larger magnitude are those indicating the control of the first three enzymes. Targeted improvements of metabolite formation through modification of all specific enzymes of biochemical reactions in complex metabolic networks would be in progress.