Table 2. Newly activated reactions in response to reaction knock down.
| Activated Enzymes | Against in silico knocked down of reaction(s)* | Remark (Literature Survey) | Gene expression data analysis (Genes up-regulated in stress conditions) |
|---|---|---|---|
| MALS (Malate Synthase) (Rv1837c) | Cofactor Metabolism (AHMMPS, GLUTRR), Fatty acid metabolism (ACCC, ACChex, FAMPL1, FAMPL2, FAMPL3, FAMPL4, FAMPL5, FAS100, FAS120, FAS140, FAS200, FAS240_L, FAS80_L, MYC1CYC1, MYCON1, MYCSacp50, MYCSacp56, MYCSacp58), Glutamate Metabolism (GLNS), Histidine Metabolism (IGPDH), Lysine Metabolism (DHDPS), Membrane metabolism (PREPTHS, PREPTHS2), Methionine Metabolism (AHC), Other Amino Acid Metabolism(PAPR), Pantothenate and CoA Metabolism (MOHMT), Phenylalanine Tyrosine Tryptophan Metabolism (ANS, IGPS), Porphyrin Metabolism (UPP3S), Valine Leucine and Isoleucine Metabolism (ACLS, IPPS) | Reported to active against persistent state of M.tuberculosis24 | |
| CYO1b (Cytochrome c oxidase) (Rv1451 and Rv2193 and Rv2200c and Rv3043c) | Cofactor Metabolism (GLUTRR, THMDP, UDCPDP), Fatty Acid Metabolism (FAMPL1, FAMPL2, FAMPL3, FAMPL4, FAMPL5, FAS240_L, FAS260, MYC1CYC1, MYC2CYC1, MYCON1, MYCON3, MYCON4, MYCON5, MYCSacp50, MYCSacp56, MYCSacp58, PSD160), Membrane Metabolism (TRE6PS), Phenylalanine Tyrosine Tryptophan Metabolism (CHORM, DDPA), Polyprenyl Metabolism (DCPDP), Porphyrin Metabolism (G1SATi, UPP3S, UPPDC1, HMBS), Sugar Metabolism (PMANM, UAGDP), Valine Leucine and Isoleucine Metabolism (KARA2i) | Phosphate depletion (GSE14840): Up-regulated in 3 samples (Out of 6 samples). | |
| ICL (iso-citrate lyase) (Rv1915 and Rv1916) or (Rv0467) | Cofactor Metabolism (DMATT), Fatty Acid Metabolism (ACCC, ACChex, MYCSacp50, MYCSacp56, MYCSacp58, PSD160, FACOAL160), Membrane Metabolism (PREPTHS, PREPTHS2), Nucleotide Sugar Metabolism (UDPG4E), Pantothenate and CoA Metabolism (PANTS), Pentose Phosphate Pathway (RPI), Phenylalanine Tyrosine Tryptophan Metabolism (IGPS), Purine Metabolism (ADSK, RNDR1), Pyrimidine Metabolism (TRDR), Sugar Metabolism (UAGCVT), Valine Leucine and Isoleucine Metabolism (IPPMIa, IPPMIb) | Reported to active against persistent state of M. tuberculosis24; Activation facilitates fatty acid metabolism25 | |
| L_LACD3 (Lactate dehydrogenase) (Rv1872c) | Fatty Acid Metabolism (FACOAL160, FAS100, FAS120, FAS140, FAS200, FAS80_L), Glutamate Metabolism (GLUDx), Lysine Metabolism (DHDPS), Membrane Metabolism (PREPTHS, PREPTHS2), Methionine Metabolism (AHC), Pantothenate and CoA Metabolism (MOHMT, PNTK, PPCDC), Phenylalanine Tyrosine Tryptophan Metabolism (ANS, IGPS), Purine Metabolism (ADSK, ATPS4r) | ||
| GLYCL (Glycine cleavage system) (Rv1826) | Fatty Acid Metabolism (FACOAL160, FAS100, FAS120, FAS140, FAS200, FAS80_L), Glycolysis (GAPD, PGK), Pantothenate and CoA Metabolism (PANTS), Phenylalanine Tyrosine Tryptophan Metabolism (CHORM, IGPS), Purine Metabolism (RNDR1), Pyrimidine Metabolism (NDPK2, NDPK4, TRDR), Transport (NH4t), Valine Leucine and Isoleucine Metabolism (DHAD1, KARA1i) | Hypoxia (GSE9331): Up-regulated in 15 samples (Out of 50 samples). | |
| ABTA (4-aminobutyrate transaminase) (Rv2589 or Rv3290) | Glycolysis (GAPD, PGK), Transport (NH4t), Valine Leucine and Isoleucine Metabolism(IPMD, IPPMIa, IPPMIb, IPPS) | Multiple stresses(GSE10391): Up-regulated in 28 samples (out of 28 samples).Hypoxia (GSE9331): Up-regulated in 39 samples (out if 50 samples) Phosphate depletion(GSE14840): Up-regulated in 3 samples (out of 6 samples) | |
| G6PDH2 (glucose-6-phosphate dehydrogenase) (Rv1447c or Rv1121) | Glycolysis (PGI, TPI), Pentose Phosphate Pathway (RPE, TALA, TKT1, TKT2) | ||
| PGL (6-phosphogluconolactonase) (Rv1445c) | Glycolysis (PGI,TPI), Pentose Phosphate Pathway (TKT1, TKT2) | ||
| GLUDC (Glutamate decarboxylase) (Rv3432c) | Alanine and Aspartate Metabolism (ASNS1), Glycolysis (GAPD, PGK) | ||
| GND (phosphogluconate dehydrogenase) (Rv1844c or Rv1122) | Pentose Phosphate Pathway (RPE, TKT1, TKT2) | ||
| NDPK6 (nucleoside di-phosphate kinase ATPdUDP) (Rv2445c) | Pantothenate and CoA Metabolism (MOHMT), Purine Metabolis (PANTS) | Knock down of Ndk significantly reduced M. tuberculosis persistence in lungs of infected mouse27 | |
| GCCb (glycine cleavage complex) (Rv2211c) | Phenylalanine Tyrosine Tryptophan Metabolism (ANPRT), Valine Leucine and Isoleucine Metabolism (ACLS) | Activity of gcvB increased in non-replicating persistence28. | |
| L_LACD (L-Lactate dehydrogenase irreversible) (Rv0694) | Membrane Metabolism (TRE6PS), Phenylalanine Tyrosine Tryptophan Metabolism (CHORM) | ||
| HPPK (2-amino-4-hydroxy-6-hydroxymethyldihydropteridine di-phosphokinase) (Rv3606c) | Folate Metabolism (DHNPA2, DHPS2) | ||
| DHORD2 (dihydoorotic acid dehydrogenase quinone8) (Rv2139) | Glycolysis(PGK), Histidine Metabolism (IG3PS) | ||
| DESAT18 (stearoyl-CoA desaturase) (Rv1094 or Rv0824c) | Fatty Acid Metabolism (FACOAL181, FAS181) | ||
| GCCa (glycine cleavage complex) (Rv1832) | Pyrimidine Metabolism (DHORTS) | Hypoxia(GSE9331): Up-regulated in 21 samples (out of 50 samples). | |
| P5CR (pyrroline-5-carboxylate reductase) (Rv0500) | Valine Leucine and Isoleucine Metabolism (KARA1i) | ||
| L_LACt3 (L-lactate transport) (Rv0191) | Purine Metabolism (ATPS4r) | Hypoxia(GSE9331): Up-regulated in 17 samples (out of 50 samples). | |
| PUNP7 (purine nucleoside phosphorylase Xanthosine) (Rv3307) | Purine Metabolism (ADPT) | PNP are listed among top targets for M. tuberculosis persistence29 | |
| SADT2 (Sulfate adenyltransferase) (Rv1285 and Rv1286) | Purine Metabolism (SADT) | CysD and CysN both are part of stress induced operon30. | Multiple stresses(GSE10391): Up-regulated in 7 samples (out of 28 samples). Hypoxia (GSE9331): Up-regulated in 46 and 42 samples (out of 50 samples). |
| FOLD3 (dihydropteroate synthase) (Rv1207 or Rv3608c) | Folate Metabolism (DHNPA2) | ||
| G5SD2 (glutamate-5-semialdehyde dehydrogenase) (Rv2427c) | Valine Leucine and Isoleucine Metabolism (KARA1i) | ||
| CYTBD2 (cytochrome oxidase bd menaquinol 8 2 protons) (Rv1620c and Rv1621c and Rv1622c and Rv1623c) | Glycolysis (PFK) | Required for M. tuberculosis adaptation to host immunity31. | Hypoxia(GSE9331): Up-regulated in 21 samples (out of 50 samples).Phosphate depletion(GSE14840): Up-regulated in 6 samples (out of 6 samples) |
| FACOAL161 (fatty acid CoA ligase hexadecenoate) (Rv3826 or Rv1529) | Fatty Acid Metabolism (FAS161) | ||
| FACOAL180 (fatty acid CoA ligase octadecanoate) (Rv3826 or Rv1529) | Fatty Acid Metabolism (FAS181) | ||
| ADA (Adenosine deaminase) (Rv3313c) | Purine Metabolism (PUNP5) | ||
| HXPRT (hypoxanthine phosphoribosyltransferase Hypoxanthine) (Rv3624c) | Purine Metabolism (PUNP5) | ||
| ORNt (ornithine transport) (Rv2320c) | Sugar Metabolism (GMAND) | ||
| ME1 (malic enzyme NAD) (Rv2332) | Glycolysis (GAPD, PGK, PYK) | ||
| DHNPA (dihydroneopterin aldolase) (Rv3607c) | Folate Metabolism (DHPS2) | Hypoxia(GSE9331): Up-regulated in 12 samples (out of 50 samples). | |
| DESAT16 (Palmitoyl CoA desaturase n C160CoA n C161CoA) (Rv3229c) | Fatty Acid Metabolism (FAS161) | Phosphate depletion (GSE14840): Up-regulated in 4 samples (out of 6 samples) |
*Reactions whose genes showed negative co-expression are marked in underlined bold letters.