Copper-sensitive operon repressor CsoR; Copper-sensitive repressor that has a key role in copper homeostasis. It is part of the cso operon involved in the cellular response to increasing concentrations of copper inside the bacterium, which can be highly toxic. In the presence of copper, CsoR fully dissociates from the promoter in the cso operon, leading to the transcription of its genes. Binds to a GC-rich pseudopallindromic sequence, 5'-GTAGCCCACCCCCAGTGGGGTGGGA-3', in the cso promoter region.

Two component transcriptional regulatory protein DevR (probably LuxR/UhpA-family); Member of the two-component regulatory system DevR/DevS (also called DosR/DosS) involved in onset of the dormancy response. Regulates an approximately 48-member regulon. When phosphorylated binds and activates the promoter of DevR regulon genes in response to hypoxia. The presence of target DNA increases stability of phospho-DevR in vitro. Activates its own transcription under hypoxic but not aerobic conditions, probably binds as a dimer to tandem binding sites within the devR and hspX promoters. Accepts [...]

Rv2847c, (MTCY24A1.10), len: 405 aa. Possible cysG,multifunctional enzyme, siroheme synthase containing uroporphyrin-III c-methyltransferase, precorrin-2 oxidase and ferrochelatase. C-terminus highly similar to many uroporphyrin-III c-methyltransferases e.g. Q51720|COBA uroporphyrinogen III methyltransferase from Propionibacterium freudenreichii (257 aa), FASTA scores: opt: 776, E(): 1.5e-39, (48.95% identity in 243 aa overlap); Q9HMY4|UROM|VNG2331G S-adenosyl-L-methionine:uroporphyrinogen III methyltransferase from Halobacterium sp. strain NRC-1 (246 aa), FASTA scores: opt: 704, E(): [...]

Uroporphyrinogen III methyltransferase / synthase; Rv0511, (MTCY21C8.02), len: 565 aa. Probable hemD (alternate gene name: cysG), uroporphyrin-III C-methyltransferase, highly similar to others e.g. CAC31936.1|AL583925 possible uroporphyrin-III C-methyltransferase from Mycobacterium leprae (563 aa); and S72909|CYSG from Mycobacterium leprae (472 aa), FASTA scores: opt: 1946, E(): 0, (83.3% identity in 472 aa overlap); T36265|5123662|CAB45351.1|AL079345 probable uroporphyrin-III C-methyltransferase from Streptomyces coelicolor (565 aa); and similar to others e.g. AAK00606.1|AF221100_3|AF [...]

Rv2847c, (MTCY24A1.10), len: 405 aa. Possible cysG,multifunctional enzyme, siroheme synthase containing uroporphyrin-III c-methyltransferase, precorrin-2 oxidase and ferrochelatase. C-terminus highly similar to many uroporphyrin-III c-methyltransferases e.g. Q51720|COBA uroporphyrinogen III methyltransferase from Propionibacterium freudenreichii (257 aa), FASTA scores: opt: 776, E(): 1.5e-39, (48.95% identity in 243 aa overlap); Q9HMY4|UROM|VNG2331G S-adenosyl-L-methionine:uroporphyrinogen III methyltransferase from Halobacterium sp. strain NRC-1 (246 aa), FASTA scores: opt: 704, E(): [...]

2-isopropylmalate synthase LeuA (alpha-isopropylmalate synthase) (alpha-IPM synthetase) (IPMS); Catalyzes the condensation of the acetyl group of acetyl-CoA with 3-methyl-2-oxobutanoate (2-oxoisovalerate) to form 3-carboxy-3- hydroxy-4-methylpentanoate (2-isopropylmalate).

Two component transcriptional regulatory protein DevR (probably LuxR/UhpA-family); Member of the two-component regulatory system DevR/DevS (also called DosR/DosS) involved in onset of the dormancy response. Regulates an approximately 48-member regulon. When phosphorylated binds and activates the promoter of DevR regulon genes in response to hypoxia. The presence of target DNA increases stability of phospho-DevR in vitro. Activates its own transcription under hypoxic but not aerobic conditions, probably binds as a dimer to tandem binding sites within the devR and hspX promoters. Accepts [...]

Copper-sensitive operon repressor CsoR; Copper-sensitive repressor that has a key role in copper homeostasis. It is part of the cso operon involved in the cellular response to increasing concentrations of copper inside the bacterium, which can be highly toxic. In the presence of copper, CsoR fully dissociates from the promoter in the cso operon, leading to the transcription of its genes. Binds to a GC-rich pseudopallindromic sequence, 5'-GTAGCCCACCCCCAGTGGGGTGGGA-3', in the cso promoter region.

Fructose 1,6-bisphosphatase GlpX; Catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate. Seems to be the major FBPase of M.tuberculosis and to play a key role in gluconeogenesis for conversion of lipid carbon into cell wall glycans. Does not display activity against inositol 1-phosphate.

6,7-dimethyl-8-ribityllumazine synthase; Catalyzes the formation of 6,7-dimethyl-8-ribityllumazine by condensation of 5-amino-6-(D-ribitylamino)uracil with 3,4-dihydroxy-2- butanone 4-phosphate. This is the penultimate step in the biosynthesis of riboflavin; Belongs to the DMRL synthase family.

Uroporphyrinogen III methyltransferase / synthase; Rv0511, (MTCY21C8.02), len: 565 aa. Probable hemD (alternate gene name: cysG), uroporphyrin-III C-methyltransferase, highly similar to others e.g. CAC31936.1|AL583925 possible uroporphyrin-III C-methyltransferase from Mycobacterium leprae (563 aa); and S72909|CYSG from Mycobacterium leprae (472 aa), FASTA scores: opt: 1946, E(): 0, (83.3% identity in 472 aa overlap); T36265|5123662|CAB45351.1|AL079345 probable uroporphyrin-III C-methyltransferase from Streptomyces coelicolor (565 aa); and similar to others e.g. AAK00606.1|AF221100_3|AF [...]

Rv2847c, (MTCY24A1.10), len: 405 aa. Possible cysG,multifunctional enzyme, siroheme synthase containing uroporphyrin-III c-methyltransferase, precorrin-2 oxidase and ferrochelatase. C-terminus highly similar to many uroporphyrin-III c-methyltransferases e.g. Q51720|COBA uroporphyrinogen III methyltransferase from Propionibacterium freudenreichii (257 aa), FASTA scores: opt: 776, E(): 1.5e-39, (48.95% identity in 243 aa overlap); Q9HMY4|UROM|VNG2331G S-adenosyl-L-methionine:uroporphyrinogen III methyltransferase from Halobacterium sp. strain NRC-1 (246 aa), FASTA scores: opt: 704, E(): [...]

Uroporphyrinogen III methyltransferase / synthase; Rv0511, (MTCY21C8.02), len: 565 aa. Probable hemD (alternate gene name: cysG), uroporphyrin-III C-methyltransferase, highly similar to others e.g. CAC31936.1|AL583925 possible uroporphyrin-III C-methyltransferase from Mycobacterium leprae (563 aa); and S72909|CYSG from Mycobacterium leprae (472 aa), FASTA scores: opt: 1946, E(): 0, (83.3% identity in 472 aa overlap); T36265|5123662|CAB45351.1|AL079345 probable uroporphyrin-III C-methyltransferase from Streptomyces coelicolor (565 aa); and similar to others e.g. AAK00606.1|AF221100_3|AF [...]

3,4-dihydroxy-2-butanone 4-phosphate synthase; Catalyzes the conversion of D-ribulose 5-phosphate to formate and 3,4-dihydroxy-2-butanone 4-phosphate; In the N-terminal section; belongs to the DHBP synthase family.

Uroporphyrinogen III methyltransferase / synthase; Rv0511, (MTCY21C8.02), len: 565 aa. Probable hemD (alternate gene name: cysG), uroporphyrin-III C-methyltransferase, highly similar to others e.g. CAC31936.1|AL583925 possible uroporphyrin-III C-methyltransferase from Mycobacterium leprae (563 aa); and S72909|CYSG from Mycobacterium leprae (472 aa), FASTA scores: opt: 1946, E(): 0, (83.3% identity in 472 aa overlap); T36265|5123662|CAB45351.1|AL079345 probable uroporphyrin-III C-methyltransferase from Streptomyces coelicolor (565 aa); and similar to others e.g. AAK00606.1|AF221100_3|AF [...]

6,7-dimethyl-8-ribityllumazine synthase; Catalyzes the formation of 6,7-dimethyl-8-ribityllumazine by condensation of 5-amino-6-(D-ribitylamino)uracil with 3,4-dihydroxy-2- butanone 4-phosphate. This is the penultimate step in the biosynthesis of riboflavin; Belongs to the DMRL synthase family.

2-isopropylmalate synthase LeuA (alpha-isopropylmalate synthase) (alpha-IPM synthetase) (IPMS); Catalyzes the condensation of the acetyl group of acetyl-CoA with 3-methyl-2-oxobutanoate (2-oxoisovalerate) to form 3-carboxy-3- hydroxy-4-methylpentanoate (2-isopropylmalate).

Rv2847c, (MTCY24A1.10), len: 405 aa. Possible cysG,multifunctional enzyme, siroheme synthase containing uroporphyrin-III c-methyltransferase, precorrin-2 oxidase and ferrochelatase. C-terminus highly similar to many uroporphyrin-III c-methyltransferases e.g. Q51720|COBA uroporphyrinogen III methyltransferase from Propionibacterium freudenreichii (257 aa), FASTA scores: opt: 776, E(): 1.5e-39, (48.95% identity in 243 aa overlap); Q9HMY4|UROM|VNG2331G S-adenosyl-L-methionine:uroporphyrinogen III methyltransferase from Halobacterium sp. strain NRC-1 (246 aa), FASTA scores: opt: 704, E(): [...]

Bifunctional enzyme MbtA: salicyl-AMP ligase (SAL-AMP ligase) + salicyl-S-ArCP synthetase; Involved in the initial steps of the mycobactin biosynthetic pathway. Catalyzes the salicylation of the aryl carrier protein (ArCP) domain of MbtB through a two-step reaction. The first step is the ATP- dependent adenylation of salicylate to generate a salicyl-AMP intermediate. The second step is the transfer of this activated salicylate to MbtB to form a salicyl-ArCP domain thioester.

Phenyloxazoline synthase MbtB (phenyloxazoline synthetase); Involved in the initial steps of the mycobactin biosynthetic pathway. Putatively couples activated salicylic acid with serine or threonine and cyclizes this precursor to the hydroxyphenyloxazoline ring system present in this class of siderophores. Essential for growth in macrophages; Belongs to the ATP-dependent AMP-binding enzyme family. MbtB subfamily.

Bifunctional enzyme MbtA: salicyl-AMP ligase (SAL-AMP ligase) + salicyl-S-ArCP synthetase; Involved in the initial steps of the mycobactin biosynthetic pathway. Catalyzes the salicylation of the aryl carrier protein (ArCP) domain of MbtB through a two-step reaction. The first step is the ATP- dependent adenylation of salicylate to generate a salicyl-AMP intermediate. The second step is the transfer of this activated salicylate to MbtB to form a salicyl-ArCP domain thioester.

Polyketide synthetase MbtD (polyketide synthase); Rv2381c, (MTCY22H8.04), len: 1004 aa. MbtD,polyketide synthase (see citations below), similar in part to several synthases e.g. Q03132|ERY2_SACER|ERYA erythronolide synthase, modules 3 and 4 from Saccharopolyspora erythraea (Streptomyces erythraeus) (3567 aa), FASTA scores: opt: 971, E(): 1e-46, (29.35% identity in 1043 aa overlap); Q9F829|megaii megalomicin 6-deoxyerythronolide B synthase 2 from Micromonospora megalomicea subsp. nigra (3562 aa), FASTA scores: opt: 787,E(): 2.4e-36, (29.35% identity in 1032 aa overlap); Q9L4W4|NYSB poly [...]

Bifunctional enzyme MbtA: salicyl-AMP ligase (SAL-AMP ligase) + salicyl-S-ArCP synthetase; Involved in the initial steps of the mycobactin biosynthetic pathway. Catalyzes the salicylation of the aryl carrier protein (ArCP) domain of MbtB through a two-step reaction. The first step is the ATP- dependent adenylation of salicylate to generate a salicyl-AMP intermediate. The second step is the transfer of this activated salicylate to MbtB to form a salicyl-ArCP domain thioester.

Rv2380c, (MTCY22H8.05), len: 1682 aa. MbtE, peptide synthetase (see citations below), similar in part to several synthases e.g. O07944|SNBDE pristinamycin I synthase 3 and 4 from Streptomyces pristinaespiralis (4848 aa), FASTA scores: opt: 2635, E(): 1.9e-146, (36.8% identity in 1657 aa overlap); O05647|SNBDE virginiamycin S synthetase (fragment) from Streptomyces virginiae (1997 aa) FASTA scores: opt: 2580, E(): 1.6e-143, (40.65% identity in 1163 aa overlap); Q9R9I2|DHBF protein involved in siderophore production from Bacillus subtilis (2378 aa),FASTA scores: opt: 2388, E(): 3.6e-132, [...]

Bifunctional enzyme MbtA: salicyl-AMP ligase (SAL-AMP ligase) + salicyl-S-ArCP synthetase; Involved in the initial steps of the mycobactin biosynthetic pathway. Catalyzes the salicylation of the aryl carrier protein (ArCP) domain of MbtB through a two-step reaction. The first step is the ATP- dependent adenylation of salicylate to generate a salicyl-AMP intermediate. The second step is the transfer of this activated salicylate to MbtB to form a salicyl-ArCP domain thioester.

Putative conserved protein MbtH; Could be involved in mycobactin synthesis.

Bifunctional enzyme MbtA: salicyl-AMP ligase (SAL-AMP ligase) + salicyl-S-ArCP synthetase; Involved in the initial steps of the mycobactin biosynthetic pathway. Catalyzes the salicylation of the aryl carrier protein (ArCP) domain of MbtB through a two-step reaction. The first step is the ATP- dependent adenylation of salicylate to generate a salicyl-AMP intermediate. The second step is the transfer of this activated salicylate to MbtB to form a salicyl-ArCP domain thioester.

Isochorismate synthase MbtI; Involved in the incorporation of salicylate into the virulence-conferring salicylate-based siderophore mycobactin. Catalyzes the initial conversion of chorismate to yield the intermediate isochorismate (isochorismate synthase activity), and the subsequent elimination of the enolpyruvyl side chain to give salicylate (isochorismate pyruvate-lyase activity). In the absence of magnesium, MbtI displays a chorismate mutase activity and converts chorismate to prephenate.

Bifunctional enzyme MbtA: salicyl-AMP ligase (SAL-AMP ligase) + salicyl-S-ArCP synthetase; Involved in the initial steps of the mycobactin biosynthetic pathway. Catalyzes the salicylation of the aryl carrier protein (ArCP) domain of MbtB through a two-step reaction. The first step is the ATP- dependent adenylation of salicylate to generate a salicyl-AMP intermediate. The second step is the transfer of this activated salicylate to MbtB to form a salicyl-ArCP domain thioester.

Rv2385, (MTCY253.36c), len: 306 aa. Putative mbtJ,acetyl hydrolase (see citations below), showing some similarity with various hydrolases including acetyl hydrolases e.g. Q9ZBM4|MLCB1450.08|ML0314 putative hydrolase/esterase from Mycobacterium leprae (335 aa),FASTA scores: opt: 449, E(): 6.7e-21, (33.85% identity in 313 aa overlap); AAK47950|MT3591 Esterase from M. tuberculosis strain CDC1551 (327 aa), FASTA scores: opt: 469, E(): 3.6e-22, (35% identity in 283 aa overlap); Q9X8J4|SCE9.22 putative esterase from Streptomyces coelicolor (266 aa), FASTA scores: opt: 430,E(): 8.5e-20,(38% i [...]

Phenyloxazoline synthase MbtB (phenyloxazoline synthetase); Involved in the initial steps of the mycobactin biosynthetic pathway. Putatively couples activated salicylic acid with serine or threonine and cyclizes this precursor to the hydroxyphenyloxazoline ring system present in this class of siderophores. Essential for growth in macrophages; Belongs to the ATP-dependent AMP-binding enzyme family. MbtB subfamily.

Bifunctional enzyme MbtA: salicyl-AMP ligase (SAL-AMP ligase) + salicyl-S-ArCP synthetase; Involved in the initial steps of the mycobactin biosynthetic pathway. Catalyzes the salicylation of the aryl carrier protein (ArCP) domain of MbtB through a two-step reaction. The first step is the ATP- dependent adenylation of salicylate to generate a salicyl-AMP intermediate. The second step is the transfer of this activated salicylate to MbtB to form a salicyl-ArCP domain thioester.

Phenyloxazoline synthase MbtB (phenyloxazoline synthetase); Involved in the initial steps of the mycobactin biosynthetic pathway. Putatively couples activated salicylic acid with serine or threonine and cyclizes this precursor to the hydroxyphenyloxazoline ring system present in this class of siderophores. Essential for growth in macrophages; Belongs to the ATP-dependent AMP-binding enzyme family. MbtB subfamily.

Polyketide synthetase MbtD (polyketide synthase); Rv2381c, (MTCY22H8.04), len: 1004 aa. MbtD,polyketide synthase (see citations below), similar in part to several synthases e.g. Q03132|ERY2_SACER|ERYA erythronolide synthase, modules 3 and 4 from Saccharopolyspora erythraea (Streptomyces erythraeus) (3567 aa), FASTA scores: opt: 971, E(): 1e-46, (29.35% identity in 1043 aa overlap); Q9F829|megaii megalomicin 6-deoxyerythronolide B synthase 2 from Micromonospora megalomicea subsp. nigra (3562 aa), FASTA scores: opt: 787,E(): 2.4e-36, (29.35% identity in 1032 aa overlap); Q9L4W4|NYSB poly [...]

Phenyloxazoline synthase MbtB (phenyloxazoline synthetase); Involved in the initial steps of the mycobactin biosynthetic pathway. Putatively couples activated salicylic acid with serine or threonine and cyclizes this precursor to the hydroxyphenyloxazoline ring system present in this class of siderophores. Essential for growth in macrophages; Belongs to the ATP-dependent AMP-binding enzyme family. MbtB subfamily.

Rv2380c, (MTCY22H8.05), len: 1682 aa. MbtE, peptide synthetase (see citations below), similar in part to several synthases e.g. O07944|SNBDE pristinamycin I synthase 3 and 4 from Streptomyces pristinaespiralis (4848 aa), FASTA scores: opt: 2635, E(): 1.9e-146, (36.8% identity in 1657 aa overlap); O05647|SNBDE virginiamycin S synthetase (fragment) from Streptomyces virginiae (1997 aa) FASTA scores: opt: 2580, E(): 1.6e-143, (40.65% identity in 1163 aa overlap); Q9R9I2|DHBF protein involved in siderophore production from Bacillus subtilis (2378 aa),FASTA scores: opt: 2388, E(): 3.6e-132, [...]

Phenyloxazoline synthase MbtB (phenyloxazoline synthetase); Involved in the initial steps of the mycobactin biosynthetic pathway. Putatively couples activated salicylic acid with serine or threonine and cyclizes this precursor to the hydroxyphenyloxazoline ring system present in this class of siderophores. Essential for growth in macrophages; Belongs to the ATP-dependent AMP-binding enzyme family. MbtB subfamily.

Putative conserved protein MbtH; Could be involved in mycobactin synthesis.

Phenyloxazoline synthase MbtB (phenyloxazoline synthetase); Involved in the initial steps of the mycobactin biosynthetic pathway. Putatively couples activated salicylic acid with serine or threonine and cyclizes this precursor to the hydroxyphenyloxazoline ring system present in this class of siderophores. Essential for growth in macrophages; Belongs to the ATP-dependent AMP-binding enzyme family. MbtB subfamily.

Isochorismate synthase MbtI; Involved in the incorporation of salicylate into the virulence-conferring salicylate-based siderophore mycobactin. Catalyzes the initial conversion of chorismate to yield the intermediate isochorismate (isochorismate synthase activity), and the subsequent elimination of the enolpyruvyl side chain to give salicylate (isochorismate pyruvate-lyase activity). In the absence of magnesium, MbtI displays a chorismate mutase activity and converts chorismate to prephenate.