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

Fang, Xin; Wallqvist, Anders; Reifman, Jaques

doi:10.1186/1752-0509-4-160

BMC Systems Biology

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, 52–57]
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, 52–57]
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, 52–57]
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, 52–57]
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

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).

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ISSN: 1752-0509

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