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Table 2 Summary of modifications to correct gene essentiality predictions after Step III.

From: Development and analysis of an in vivo-compatible metabolic network of Mycobacterium tuberculosis

Gene Group No. Gene No. Gene Locus Gene Name FP/FN Pathway Function/Reaction Modification to Correct the False Gene Essentiality Prediction Supporting Literature (References)
1 1 Rv1099c Rv1099c FN Glycolysis/gluconeogenesis Convert fructose-1,6-bisphosphate into fructose-6-phosphate (1) Blocked the uptake of glucose from environment [8, 28, 32, 5257]
2 2 Rv2702 ppgK FN Glycolysis/gluconeogenesis Conversion between glucose-6-phosphate and glucose (1) Blocked the conversion from maltose to glucose and blocked the uptake of glucose
(2) Blocked the conversion between maltose and trehalose and blocked the uptake of glucose
[8, 28, 32, 5257]
3 3
4
5
Rv1350
Rv1483
Rv2947c
fabG2
inhA
pks15
FP
FP
FP
Fatty acid metabolism Synthesis of fatty acids (1) Allowed the uptakes of the following fatty acids: hexadecanoate, octadecanoate, octanoate, dodecanoate, arachidic acid, and hexacosanoate [8, 28, 32, 5257]
4 6 Rv2503c scoB FP Fatty acid metabolism Functions as 3-oxoacid CoA-transferase (1) Let the reaction catalyzed by acetyl-CoA:acetoacetyl-CoA transferase be reversible  
5 7 Rv3229c desA3 FN Fatty acid metabolism Palmitoyl-CoA desaturation (1) Blocked the synthesis of hexadecenoate [8, 28, 32, 5257]
6 8 Rv1185c fadD21 FN Fatty acid metabolism Synthesis of fatty acid-CoA (1) Blocked the ability of fadD9 (Rv2590), fadD24 (Rv1529), and fadD23 (Rv3826) to catalyze the synthesis of fatty acid-CoA  
7 9 Rv0098 Rv0098 FN Fatty acid metabolism Mycolic acid synthesis (1) Blocked the ability of fabG1 (Rv1483) to catalyze the same reaction  
8 10 Rv2483c plsC FN Fatty acid metabolism Synthesis of 1,2-diacyl-sn-glycerol 3-phosphate (a phospholipid) (1) Blocked the ability of Rv2182c to catalyze the same reaction  
9 11 Rv1416 ribH FP Vitamin and cofactor metabolism Synthesis of riboflavin (1) Removed riboflavin and flavin mononucleotide (FMN) from the biomass objective function  
10 12 Rv1412 ribC FP Vitamin and cofactor metabolism Synthesis of riboflavin (1) Removed riboflavin and FMN from the biomass objective function  
11 13 Rv2671 ribD FP Vitamin and cofactor metabolism Synthesis of riboflavin precursor (1) Removed riboflavin and FMN from the biomass objective function  
12 14 Rv2786c ribF FP Vitamin and cofactor metabolism Synthesis of FMN from riboflavin (1) Removed FMN from the biomass objective function  
13 15 Rv2421c Rv2421c FP Vitamin and cofactor metabolism Synthesis of deamino-NAD+ (1) Removed nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) from the biomass objective function  
14 16 Rv1596 nadC FP Vitamin and cofactor metabolism Functions as nicotinate-nucleotide diphosphorylase (1) Removed NAD and NADP from the biomass objective function  
15 17 Rv3215 entC FP Vitamin and cofactor metabolism Synthesis of isochorismate (1) Removed menaquinol 8 from the biomass objective fucntion  
16 18 Rv1568 bioA FN Vitamin and cofactor metabolism Synthesis of a precursor of biotin (1) Added biotinyl-5'-AMP to the biomass objective function  
17 19 Rv1569 bioF FN Vitamin and cofactor metabolism Synthesis of a precursor of biotin (1) Added biotinyl-5'-AMP to the biomass objective function and blocked the ability of bioF2 (Rv0032) to catalyze the same reaction  
18 20 Rv1589 bioB FN Vitamin and cofactor metabolism Synthesis of biotin (1) Added biotinyl-5'-AMP to the biomass objective function  
19 21 Rv2211c gcvT FN Vitamin and cofactor metabolism Conversion between 5-formyltetrahydrofolate and 5,10-methenyltetrahydrofolate (1) Added the metabolite 5-formyltetrahydrofolate to the biomass objective function  
20 22 Rv3001c ilvC FP Amino acid metabolism Synthesis of 2,3-dihydroxy-3-methylbutanoate and 2,3-dihydroxy-3-methylpentanoate (1) Allowed the uptakes of isoleucine and valine [61]
21 23 Rv3002c ilvN FP Amino acid metabolism Synthesis of acetolactate (1) Allowed the uptake of valine [61]
22 24
25
26
27
Rv2220c
Rv1878
Rv2222c
Rv2860c
glnA1
glnA3
glnA2
glnA4
FP
FP
FP
FP
Amino acid metabolism Synthesis of glutamine (1) Let the reaction of glutamate synthesis from glutamine to be reversible
(2) Let the conversion to CTP and glutamate from UTP and glutamine be reversible
 
23 28 Rv3754 tyrA FP Amino acid metabolism Functions as prephenate dehydrogenase (1) Allowed the uptake of tyrosine  
24 29 Rv3042c serB2 FN Amino acid metabolism Remove a phosphate group from phosphoserine to produce serine (1) Blocked the ability of serB (Rv0505c) to catalyze the same reaction  
25 30 Rv2231c cobC FN Amino acid metabolism Convert glutamate into histidinol-phosphate (1) Blocked the ability of hisC2 (Rv3772) and hisC (Rv1600) to catalyze the conversion  
26 31 Rv2945c lppX FN Transport Transport phthiocerol dimycocerosate A and phenol phthiocerol dimycocerosate out of the cell (1) Added extracellular phthiocerol dimycocerosate A to the biomass objective function
(2) Added extracellular phenol phthiocerol dimycocerosate to the biomass objective function
[62]
27 32
33
34
Rv1236
Rv1237
Rv1238
sugA
sugB
sugC
FN Transport Transport of glucose, maltoheptaose, maltose, ribose, trehalose, and xylose into cell (1) Allowed xylose uptake and added xylose to the biomass objective function  
28 35 Rv3236c kefB FN Transport Transport of K+ and Na+ into the cell (1) Blocked the function of potassium ABC transporter
(2) Blocked the function of the Na+ antiporter
 
29 36 Rv1699 pyrG FP Nucleotide metabolism Synthesis of CTP from UTP (1) Allowed the uptake of cytidine  
30 37 Rv1385 pyrF FP Nucleotide metabolism Functions as orotidine-5'-phosphate decarboxylase (1) Allowed the uptake of cytidine  
31 38 Rv2139 pyrD FP Nucleotide metabolism Functions as dihydroorotic acid dehydrogenase (1) Allowed the uptake of cytidine  
32 39 Rv3393 iunH FP Nucleotide metabolism Hydrolysis of inosine (1) Let the reaction catalyzed by ribokinase be reversible  
33 40 Rv2465c rpi FP Pentose phosphate pathway Functions as ribose-5-phosphate isomerase (1) Allowed the secretion of D-arabinose  
34 41 Rv3628 ppa FP Multiple pathways Functions as inorganic diphosphatase (1) let the reaction catalyzed by nucleoside triphosphate tripolyhydrolase of deoxy-GTP (dGTP) to be reversible  
35 42 Rv3588c Rv3588c FN Multiple pathways Conversion between carboxylic acid and carbon dioxide (1) Blocked the ability of Rv3273 to catalyze the same reaction  
  1. Of the 25 genes that were incorrectly predicted to be non-essential (FN) under in vivo conditions, 18 genes were corrected and became essential in the iNJ 661v network. Of the 76 genes that were incorrectly predicted to be essential (FP) under in vivo conditions, 24 genes were corrected and became non-essential in the iNJ 661v network. We classified the overall 42 (18 + 24) genes into 35 gene groups, defined as a group of genes whose products catalyze the same reaction(s).