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PLoS Pathog. 2011 Jul;7(7):e1002091. 13C metabolic flux analysis identifies an unusual route for pyruvate dissimilation in mycobacteria which requires isocitrate lyase and carbon dioxide fixation. Beste DJ, Bonde B, Hawkins N, et al.



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ATP production rate Maximum 355.38 -R01786-R04779+2.5*R01061+R01512+R00200+2.5*R00209
+2.5*R00267+2.5*R08549-R00405+1.5*R00402+2.5*R00342
+2.5*R00214
ATP production rate Minium 345.68 -R01786-R04779+2.5*R01061+R01512+R00200+2.5*R00209
+2.5*R08549-R00405+1.5*R00402+2.5*R00342
NADPH production rate Maximum 56.22 R02736+R01528+R00267+R00214
NADPH production rate Minium 52.34 R02736+R01528
ATP production rate Maximum 351.83 -R01786-R04779+2.5*R01061+R01512+R00200+2.5*R00209
+2.5*R00267+2.5*R08549-R00405+1.5*R00402+2.5*R00342
+2.5*R00214
ATP production rate Minium 337.81 -R01786-R04779+2.5*R01061+R01512+R00200+2.5*R00209
+2.5*R08549-R00405+1.5*R00402+2.5*R00342
NADPH production rate Maximum 185.51 R02736+R01528+R00267+R00214
NADPH production rate Minium 179.9 R02736+R01528
ATP production rate Maximum 493.19 -R01786-R04779+2.5*R01061+R01512+R00200+2.5*R00209
+2.5*R00267+2.5*R08549-R00405+1.5*R00402+2.5*R00342
+2.5*R00214
ATP production rate Minium 471.09 -R01786-R04779+2.5*R01061+R01512+R00200+2.5*R00209
+2.5*R08549-R00405+1.5*R00402+2.5*R00342
NADPH production rate Maximum 10.52 R02736+R01528+R00267+R00214
NADPH production rate Minium 1.68 R02736+R01528
ATP production rate Maximum N/A -R01786-R04779+2.5*R01061+R01512+R00200+2.5*R00209
+2.5*R00267+2.5*R08549-R00405+1.5*R00402+2.5*R00342
+2.5*R00214
ATP production rate Minium N/A -R01786-R04779+2.5*R01061+R01512+R00200+2.5*R00209
+2.5*R08549-R00405+1.5*R00402+2.5*R00342
NADPH production rate Maximum 72.42 R02736+R01528+R00267+R00214
NADPH production rate Minium 67.74 R02736+R01528
ATP production rate Maximum N/A -R01786-R04779+2.5*R01061+R01512+R00200+2.5*R00209
+2.5*R00267+2.5*R08549-R00405+1.5*R00402+2.5*R00342
+2.5*R00214
ATP production rate Minium N/A -R01786-R04779+2.5*R01061+R01512+R00200+2.5*R00209
+2.5*R08549-R00405+1.5*R00402+2.5*R00342
NADPH production rate Maximum 7.33 R02736+R01528+R00267+R00214
NADPH production rate Minium 0.1 R02736+R01528
Growth Condition
Strains Mycobacterium bovis BCG(ATCC 35748)
Genotype
Culture medium Chemostat cultures were grown in Roisin’s minimal medium at a constant dilution rate of 0.03/h. Culture samples were withdrawn from the chemostat to monitor cellular dry weight, viable counts, optical density, nutrient utilization and CO2 and O2 levels were measured in the exhaust gas. After waiting five residence times at a particular dilution rate, the reactor was assumed to be at steady state if the OD, glycerol concentration,oxygen uptake rate and CO2 production rate were steady within a 15% range for 48 h.
Carbon source Glycerol
Growth rate
Case-specific description In vivo flux distribution of M.bovis BCG in glycerol limited continuous culture at fast growth rate (t= 23 h).
Growth Condition
Strains Mycobacterium bovis BCG(ATCC 35748)
Genotype Wild type.
Culture medium Chemostat cultures were grown in Roisin’s minimal medium at a constant dilution rate of 0.01/h. Culture samples were withdrawn from the chemostat to monitor cellular dry weight, viable counts, optical density, nutrient utilization and CO2 and O2 levels were measured in the exhaust gas. After waiting five residence times at a particular dilution rate, the reactor was assumed to be at steady state if the OD, glycerol concentration,oxygen uptake rate and CO2 production rate were steady within a 15% range for 48 h.
Carbon source Glycerol
Growth rate
Case-specific description Metabolic flux map corresponding to solution A for M.bovis BCG in glycerol limited continuous culture at slow growth rate(t= 69 h).The flux values cannot be determined unambiguously from the available labeling data.This flux distibutions(A) is corresponding to one of the two equally likely solutions(A and B).
Growth Condition
Strains Mycobacterium bovis BCG(ATCC 35748)
Genotype Wild type.
Culture medium Chemostat cultures were grown in Roisin’s minimal medium at a constant dilution rate of 0.01/h. Culture samples were withdrawn from the chemostat to monitor cellular dry weight, viable counts, optical density, nutrient utilization and CO2 and O2 levels were measured in the exhaust gas. After waiting five residence times at a particular dilution rate, the reactor was assumed to be at steady state if the OD, glycerol concentration,oxygen uptake rate and CO2 production rate were steady within a 15% range for 48 h.
Carbon source Glycerol
Growth rate
Case-specific description Metabolic flux map B for M.bovisBCG in glycerol limited continuous culture at slow growth rate (t= 69 h).The flux values cannot be determined unambiguously from the available labeling data. This flux distibutions(B) is corresponding to one of the two equally likely solutions(A and B).
Growth Condition
Strains Mycobacterium tuberculosis(H37Rv)
Genotype Wild type.
Culture medium Chemostat cultures were grown in Roisin’s minimal medium at a constant dilution rate of 0.01/h. Culture samples were withdrawn from the chemostat to monitor cellular dry weight, viable counts, optical density, nutrient utilization and CO2 and O2 levels were measured in the exhaust gas. After waiting five residence times at a particular dilution rate, the reactor was assumed to be at steady state if the OD, glycerol concentration,oxygen uptake rate and CO2 production rate were steady within a 15% range for 48 h.
Carbon source Glycerol
Growth rate
Case-specific description Metabolic flux map corresponding to solution A for M.tuberculosisin glycerol limited continuous culture at slow growth rate (t= 69 h). The flux values cannot be determined unambiguously from the available labeling data.This flux distibutions(A) is corresponding to one of the two equally likely solutions(A and B).
Growth Condition
Strains Mycobacterium tuberculosis(H37Rv)
Genotype Wild type.
Culture medium Chemostat cultures were grown in Roisin’s minimal medium at a constant dilution rate of 0.01/h. Culture samples were withdrawn from the chemostat to monitor cellular dry weight, viable counts, optical density, nutrient utilization and CO2 and O2 levels were measured in the exhaust gas. After waiting five residence times at a particular dilution rate, the reactor was assumed to be at steady state if the OD, glycerol concentration,oxygen uptake rate and CO2 production rate were steady within a 15% range for 48 h.
Carbon source Glycerol
Growth rate
Case-specific description Metabolic flux map B for M.tuberculosisin glycerol limited continuous culture at slow growth rate (t= 69 h).The flux values cannot be determined unambiguously from the available labeling data.This flux distibutions(B) is corresponding to one of the two equally likely solutions(A and B).
Specific Rate (mmol g-1 h-1)
Glycerol 0.74
Tween 80 0.09
CO2 0.45
Specific Rate (mmol g-1 h-1)
Glycerol 0.39
Tween 80 0.002
CO2 0.57
Specific Rate (mmol g-1 h-1)
Glycerol 0.39
Tween 80 0.002
CO2 0.57
Specific Rate (mmol g-1 h-1)
Glycerol 0.39
Tween 80 0.003
CO2 0.23
Specific Rate (mmol g-1 h-1)
Glycerol 0.39
Tween 80 0.003
CO2 0.23
Source