Collection of Manually Curated Inferences of Regulons in Prokaryotic Genomes
-- version 4.0 --

Collection of regulogs in Comamonadaceae taxonomic group

General statistics
Genomes 11
TF regulogs 72
TF regulons 316
TF binding sites 886
RNA regulogs 4
RNA regulons 26
RNA sites 50

This collection involves all regulons that were tentatively predicted by applying integrative comparative genomic approach to a single taxonomic group of closely-related genomes. To infer the regulons operated by transcription factors (TFs), we combined the identification of TF binding sites and cross-genome comparison of regulons with the analysis of the genomic and functional context of candidate target genes. To infer the regulons operated by regulatory RNAs such as riboswitches, we identified candidate RNA regulatory elements using HMM profiles and further analyzed their genomic and functional context.

Studied genomes and reconstructed regulon statistics
TF RNA Total
Genomes Regulons Sites Regulons Sites Regulons Sites
Acidovorax avenae subsp. citrulli AAC00-1 26 70 2 5 28 75
Acidovorax sp. JS42 20 73 3 5 23 78
Comamonas testosteroni KF-1 31 93 3 6 34 99
Delftia acidovorans SPH-1 45 118 3 6 48 124
Leptothrix cholodnii SP-6 19 57 2 4 21 61
Methylibium petroleiphilum PM1 25 65 2 4 27 69
Polaromonas naphthalenivorans CJ2 28 83 2 3 30 86
Polaromonas sp. JS666 32 100 2 4 34 104
Rhodoferax ferrireducens DSM 15236 26 72 2 6 28 78
Variovorax paradoxus S110 36 97 3 5 39 102
Verminephrobacter eiseniae EF01-2 28 58 2 2 30 60
Genomic distribution of regulons
Family Type Regulator Function
FUR TF Zur
1 Zur

Acidovorax avenae subsp. citrulli AAC00-1
1 Zur

Delftia acidovorans SPH-1
2 Zur

Polaromonas naphthalenivorans CJ2
1 Zur

Polaromonas sp. JS666
2 Zur

Rhodoferax ferrireducens DSM 15236
Zinc homeostasis
TF Zur2
2 Zur2

Verminephrobacter eiseniae EF01-2
1 Zur2

Leptothrix cholodnii SP-6
Zinc homeostasis
Fis TF NorR
3 NorR

Acidovorax sp. JS42
2 NorR

Comamonas testosteroni KF-1
2 NorR

Delftia acidovorans SPH-1
2 NorR

Polaromonas naphthalenivorans CJ2
2 NorR

Polaromonas sp. JS666
2 NorR

Variovorax paradoxus S110
Nitrosative stress response
TF NtrC
4 NtrC

Acidovorax avenae subsp. citrulli AAC00-1
5 NtrC

Acidovorax sp. JS42
4 NtrC

Comamonas testosteroni KF-1
4 NtrC

Delftia acidovorans SPH-1
3 NtrC

Polaromonas naphthalenivorans CJ2
3 NtrC

Polaromonas sp. JS666
3 NtrC

Rhodoferax ferrireducens DSM 15236
5 NtrC

Variovorax paradoxus S110
2 NtrC

Verminephrobacter eiseniae EF01-2
1 NtrC

Methylibium petroleiphilum PM1
3 NtrC

Leptothrix cholodnii SP-6
Nitrogen assimilation
GntR/MocR TF Aave_3430
2 Aave_3430

Acidovorax avenae subsp. citrulli AAC00-1
2 Aave_3430

Comamonas testosteroni KF-1
2 Aave_3430

Delftia acidovorans SPH-1
2 Aave_3430

Polaromonas naphthalenivorans CJ2
2 Aave_3430

Polaromonas sp. JS666
2 Aave_3430

Variovorax paradoxus S110
TF Bpro_5165
1 Bpro_5165

Polaromonas sp. JS666
TF Daci_0288
1 Daci_0288

Delftia acidovorans SPH-1
TF Daci_0595
1 Daci_0595

Acidovorax avenae subsp. citrulli AAC00-1
1 Daci_0595

Acidovorax sp. JS42
2 Daci_0595

Comamonas testosteroni KF-1
2 Daci_0595

Delftia acidovorans SPH-1
1 Daci_0595

Polaromonas naphthalenivorans CJ2
1 Daci_0595

Polaromonas sp. JS666
1 Daci_0595

Rhodoferax ferrireducens DSM 15236
1 Daci_0595

Variovorax paradoxus S110
1 Daci_0595

Methylibium petroleiphilum PM1
Metabolite transport
TF Daci_1890
1 Daci_1890

Comamonas testosteroni KF-1
1 Daci_1890

Delftia acidovorans SPH-1
TF Daci_4286
1 Daci_4286

Delftia acidovorans SPH-1
TF EutR
3 EutR

Verminephrobacter eiseniae EF01-2
Ectoine utilization
TF GabR
1 GabR

Delftia acidovorans SPH-1
1 GabR

Polaromonas naphthalenivorans CJ2
1 GabR

Rhodoferax ferrireducens DSM 15236
Gamma-aminobutyrate utilization
TF GabR2
1 GabR2

Polaromonas naphthalenivorans CJ2
1 GabR2

Polaromonas sp. JS666
1 GabR2

Rhodoferax ferrireducens DSM 15236
1 GabR2

Variovorax paradoxus S110
Gamma-aminobutyrate utilization
TF PdxQ
1 PdxQ

Delftia acidovorans SPH-1
Pyridoxine/pyridoxal homeostasis
TF PdxQ2
2 PdxQ2

Delftia acidovorans SPH-1
Metabolite transport; Pyridoxine/pyridoxal homeostasis
TF PdxQ3
1 PdxQ3

Delftia acidovorans SPH-1
1 PdxQ3

Methylibium petroleiphilum PM1
Metabolite transport; Pyridoxine/pyridoxal homeostasis
TF PdxR
1 PdxR

Comamonas testosteroni KF-1
1 PdxR

Delftia acidovorans SPH-1
Pyridoxine/pyridoxal homeostasis
TF PdxR3
2 PdxR3

Methylibium petroleiphilum PM1
Pyridoxine/pyridoxal homeostasis
TF PdxW
1 PdxW

Delftia acidovorans SPH-1
1 PdxW

Variovorax paradoxus S110
Pyridoxine/pyridoxal homeostasis
TF PdxW2
1 PdxW2

Leptothrix cholodnii SP-6
Pyridoxine/pyridoxal homeostasis
TF TauR
3 TauR

Comamonas testosteroni KF-1
3 TauR

Delftia acidovorans SPH-1
2 TauR

Variovorax paradoxus S110
3 TauR

Verminephrobacter eiseniae EF01-2
Taurine utilization
TF Vapar_1337
1 Vapar_1337

Variovorax paradoxus S110
TF Vapar_5644
1 Vapar_5644

Variovorax paradoxus S110
1 Vapar_5644

Verminephrobacter eiseniae EF01-2
TF Veis_0044
3 Veis_0044

Verminephrobacter eiseniae EF01-2
TF Veis_4721
1 Veis_4721

Verminephrobacter eiseniae EF01-2
TF YdcR
1 YdcR

Delftia acidovorans SPH-1
1 YdcR

Polaromonas naphthalenivorans CJ2
1 YdcR

Polaromonas sp. JS666
1 YdcR

Variovorax paradoxus S110
1 YdcR

Methylibium petroleiphilum PM1
2 YdcR

Leptothrix cholodnii SP-6
TF YrdX
1 YrdX

Polaromonas naphthalenivorans CJ2
1 YrdX

Variovorax paradoxus S110
1 YrdX

Methylibium petroleiphilum PM1
GntR/Others TF Aave_3515
2 Aave_3515

Acidovorax avenae subsp. citrulli AAC00-1
2 Aave_3515

Comamonas testosteroni KF-1
2 Aave_3515

Delftia acidovorans SPH-1
2 Aave_3515

Rhodoferax ferrireducens DSM 15236
2 Aave_3515

Verminephrobacter eiseniae EF01-2
TF Daci_3053
2 Daci_3053

Delftia acidovorans SPH-1
3 Daci_3053

Polaromonas sp. JS666
2 Daci_3053

Variovorax paradoxus S110
Glycolate utilization; Lactate utilization
TF Daci_3836
1 Daci_3836

Comamonas testosteroni KF-1
1 Daci_3836

Delftia acidovorans SPH-1
1 Daci_3836

Variovorax paradoxus S110
2 Daci_3836

Verminephrobacter eiseniae EF01-2
2 Daci_3836

Methylibium petroleiphilum PM1
1 Daci_3836

Leptothrix cholodnii SP-6
TF GguR
3 GguR

Acidovorax avenae subsp. citrulli AAC00-1
3 GguR

Acidovorax sp. JS42
3 GguR

Comamonas testosteroni KF-1
3 GguR

Delftia acidovorans SPH-1
2 GguR

Polaromonas naphthalenivorans CJ2
2 GguR

Polaromonas sp. JS666
3 GguR

Variovorax paradoxus S110
2 GguR

Methylibium petroleiphilum PM1
4 GguR

Leptothrix cholodnii SP-6
Glucarate utilization; Galactarate utilization; Galacturonate utilization; Glucuronate utilization
TF HutC
2 HutC

Acidovorax avenae subsp. citrulli AAC00-1
4 HutC

Comamonas testosteroni KF-1
3 HutC

Delftia acidovorans SPH-1
6 HutC

Polaromonas sp. JS666
1 HutC

Rhodoferax ferrireducens DSM 15236
2 HutC

Variovorax paradoxus S110
1 HutC

Verminephrobacter eiseniae EF01-2
Histidine utilization
TF LldR
1 LldR

Comamonas testosteroni KF-1
1 LldR

Delftia acidovorans SPH-1
2 LldR

Rhodoferax ferrireducens DSM 15236
Lactate utilization
TF MdcY
2 MdcY

Rhodoferax ferrireducens DSM 15236
2 MdcY

Methylibium petroleiphilum PM1
2 MdcY

Leptothrix cholodnii SP-6
Malonate metabolism
TF PhnF
2 PhnF

Methylibium petroleiphilum PM1
Phosphonate utilization
TF PhnR2
4 PhnR2

Polaromonas sp. JS666
2 PhnR2

Verminephrobacter eiseniae EF01-2
Phosphonoacetate utilization; Phosphonate utilization; 2-aminoethylphosphonate utilization
TF PrpR
1 PrpR

Verminephrobacter eiseniae EF01-2
Methylcitrate utilization
TF SdaR
1 SdaR

Rhodoferax ferrireducens DSM 15236
Glucarate utilization; Galactarate utilization
TF SdhR
3 SdhR

Acidovorax avenae subsp. citrulli AAC00-1
3 SdhR

Acidovorax sp. JS42
3 SdhR

Comamonas testosteroni KF-1
3 SdhR

Delftia acidovorans SPH-1
3 SdhR

Polaromonas naphthalenivorans CJ2
3 SdhR

Polaromonas sp. JS666
3 SdhR

Rhodoferax ferrireducens DSM 15236
3 SdhR

Variovorax paradoxus S110
3 SdhR

Verminephrobacter eiseniae EF01-2
3 SdhR

Methylibium petroleiphilum PM1
4 SdhR

Leptothrix cholodnii SP-6
Tricarboxylic acid cycle
TF UreR
1 UreR

Acidovorax avenae subsp. citrulli AAC00-1
2 UreR

Comamonas testosteroni KF-1
3 UreR

Delftia acidovorans SPH-1
TF UxuR2
2 UxuR2

Polaromonas naphthalenivorans CJ2
4 UxuR2

Polaromonas sp. JS666
5 UxuR2

Variovorax paradoxus S110
3 UxuR2

Verminephrobacter eiseniae EF01-2
Glucuronate utilization; Galacturonate utilization
TF UxuR3
2 UxuR3

Polaromonas sp. JS666
1 UxuR3

Variovorax paradoxus S110
1 UxuR3

Verminephrobacter eiseniae EF01-2
Glucuronate utilization
TF VanR
2 VanR

Comamonas testosteroni KF-1
1 VanR

Delftia acidovorans SPH-1
1 VanR

Polaromonas naphthalenivorans CJ2
1 VanR

Polaromonas sp. JS666
1 VanR

Variovorax paradoxus S110
1 VanR

Verminephrobacter eiseniae EF01-2
Vanillate utilization
HrcA TF HrcA
2 HrcA

Acidovorax avenae subsp. citrulli AAC00-1
2 HrcA

Acidovorax sp. JS42
2 HrcA

Comamonas testosteroni KF-1
2 HrcA

Delftia acidovorans SPH-1
2 HrcA

Polaromonas naphthalenivorans CJ2
2 HrcA

Polaromonas sp. JS666
2 HrcA

Rhodoferax ferrireducens DSM 15236
2 HrcA

Variovorax paradoxus S110
2 HrcA

Verminephrobacter eiseniae EF01-2
2 HrcA

Methylibium petroleiphilum PM1
2 HrcA

Leptothrix cholodnii SP-6
Heat shock response
LacI TF Bpro_5109
1 Bpro_5109

Polaromonas sp. JS666
1 Bpro_5109

Verminephrobacter eiseniae EF01-2
Sugar utilization
TF FruR2
2 FruR2

Acidovorax avenae subsp. citrulli AAC00-1
2 FruR2

Delftia acidovorans SPH-1
Fructose utilization
TF GntR
2 GntR

Acidovorax avenae subsp. citrulli AAC00-1
2 GntR

Acidovorax sp. JS42
2 GntR

Comamonas testosteroni KF-1
2 GntR

Delftia acidovorans SPH-1
2 GntR

Polaromonas naphthalenivorans CJ2
2 GntR

Rhodoferax ferrireducens DSM 15236
2 GntR

Variovorax paradoxus S110
2 GntR

Leptothrix cholodnii SP-6
Gluconate utilization
TF GudR
2 GudR

Acidovorax avenae subsp. citrulli AAC00-1
1 GudR

Polaromonas naphthalenivorans CJ2
4 GudR

Polaromonas sp. JS666
2 GudR

Methylibium petroleiphilum PM1
Glucarate utilization
TF RbsR
1 RbsR

Acidovorax avenae subsp. citrulli AAC00-1
1 RbsR

Variovorax paradoxus S110
Ribose utilization
LexA TF LexA
8 LexA

Acidovorax avenae subsp. citrulli AAC00-1
6 LexA

Acidovorax sp. JS42
5 LexA

Comamonas testosteroni KF-1
5 LexA

Delftia acidovorans SPH-1
4 LexA

Polaromonas naphthalenivorans CJ2
7 LexA

Polaromonas sp. JS666
6 LexA

Rhodoferax ferrireducens DSM 15236
6 LexA

Variovorax paradoxus S110
3 LexA

Verminephrobacter eiseniae EF01-2
8 LexA

Methylibium petroleiphilum PM1
4 LexA

Leptothrix cholodnii SP-6
SOS response
LysR TF MetR
2 MetR

Acidovorax sp. JS42
2 MetR

Comamonas testosteroni KF-1
1 MetR

Delftia acidovorans SPH-1
2 MetR

Variovorax paradoxus S110
2 MetR

Verminephrobacter eiseniae EF01-2
Methionine biosynthesis
MerR TF CadR-PbrR
1 CadR-PbrR

Acidovorax avenae subsp. citrulli AAC00-1
5 CadR-PbrR

Acidovorax sp. JS42
5 CadR-PbrR

Comamonas testosteroni KF-1
2 CadR-PbrR

Delftia acidovorans SPH-1
1 CadR-PbrR

Polaromonas naphthalenivorans CJ2
1 CadR-PbrR

Polaromonas sp. JS666
1 CadR-PbrR

Rhodoferax ferrireducens DSM 15236
1 CadR-PbrR

Variovorax paradoxus S110
2 CadR-PbrR

Verminephrobacter eiseniae EF01-2
2 CadR-PbrR

Methylibium petroleiphilum PM1
Lead resistance; Cadmium resistance
TF CueR
2 CueR

Acidovorax avenae subsp. citrulli AAC00-1
4 CueR

Acidovorax sp. JS42
1 CueR

Comamonas testosteroni KF-1
2 CueR

Delftia acidovorans SPH-1
2 CueR

Polaromonas naphthalenivorans CJ2
4 CueR

Polaromonas sp. JS666
2 CueR

Rhodoferax ferrireducens DSM 15236
3 CueR

Variovorax paradoxus S110
5 CueR

Methylibium petroleiphilum PM1
Copper resistance
TF LiuR
3 LiuR

Acidovorax avenae subsp. citrulli AAC00-1
4 LiuR

Acidovorax sp. JS42
5 LiuR

Comamonas testosteroni KF-1
4 LiuR

Delftia acidovorans SPH-1
5 LiuR

Polaromonas naphthalenivorans CJ2
5 LiuR

Polaromonas sp. JS666
4 LiuR

Rhodoferax ferrireducens DSM 15236
1 LiuR

Variovorax paradoxus S110
4 LiuR

Leptothrix cholodnii SP-6
Branched-chain amino acid degradation
TF LiuR2
2 LiuR2

Rhodoferax ferrireducens DSM 15236
Acyclic terpenes degradation
TF MerR
2 MerR

Acidovorax sp. JS42
1 MerR

Comamonas testosteroni KF-1
1 MerR

Delftia acidovorans SPH-1
2 MerR

Polaromonas sp. JS666
1 MerR

Methylibium petroleiphilum PM1
Mercury resistance
TF NmlR
1 NmlR

Polaromonas naphthalenivorans CJ2
1 NmlR

Rhodoferax ferrireducens DSM 15236
Carbonyl stress response
TF SoxR
3 SoxR

Acidovorax avenae subsp. citrulli AAC00-1
2 SoxR

Comamonas testosteroni KF-1
3 SoxR

Delftia acidovorans SPH-1
2 SoxR

Polaromonas sp. JS666
2 SoxR

Variovorax paradoxus S110
Superoxide stress response
ModE TF FdsR
2 FdsR

Variovorax paradoxus S110
2 FdsR

Methylibium petroleiphilum PM1
Formate oxydation
TF ModE
1 ModE

Acidovorax avenae subsp. citrulli AAC00-1
2 ModE

Acidovorax sp. JS42
2 ModE

Comamonas testosteroni KF-1
2 ModE

Delftia acidovorans SPH-1
2 ModE

Rhodoferax ferrireducens DSM 15236
1 ModE

Verminephrobacter eiseniae EF01-2
Molybdenum homeostasis
TF ModE2
2 ModE2

Comamonas testosteroni KF-1
2 ModE2

Delftia acidovorans SPH-1
2 ModE2

Polaromonas sp. JS666
1 ModE2

Variovorax paradoxus S110
1 ModE2

Verminephrobacter eiseniae EF01-2
Molybdopterin biosynthesis
TF ModE3
2 ModE3

Acidovorax sp. JS42
2 ModE3

Polaromonas naphthalenivorans CJ2
2 ModE3

Polaromonas sp. JS666
2 ModE3

Rhodoferax ferrireducens DSM 15236
1 ModE3

Variovorax paradoxus S110
1 ModE3

Methylibium petroleiphilum PM1
2 ModE3

Leptothrix cholodnii SP-6
Tungsten homeostasis
NadQ TF NadQ
2 NadQ

Comamonas testosteroni KF-1
2 NadQ

Delftia acidovorans SPH-1
NAD biosynthesis
NikR TF NikR
1 NikR

Delftia acidovorans SPH-1
2 NikR

Methylibium petroleiphilum PM1
Nickel homeostasis
NrdR TF NrdR
1 NrdR

Acidovorax avenae subsp. citrulli AAC00-1
2 NrdR

Acidovorax sp. JS42
1 NrdR

Comamonas testosteroni KF-1
1 NrdR

Delftia acidovorans SPH-1
1 NrdR

Polaromonas naphthalenivorans CJ2
1 NrdR

Polaromonas sp. JS666
2 NrdR

Rhodoferax ferrireducens DSM 15236
1 NrdR

Variovorax paradoxus S110
1 NrdR

Verminephrobacter eiseniae EF01-2
2 NrdR

Methylibium petroleiphilum PM1
1 NrdR

Leptothrix cholodnii SP-6
Deoxyribonucleotide biosynthesis
NrtR TF NrtR
1 NrtR

Acidovorax avenae subsp. citrulli AAC00-1
2 NrtR

Delftia acidovorans SPH-1
2 NrtR

Polaromonas naphthalenivorans CJ2
2 NrtR

Variovorax paradoxus S110
NAD biosynthesis
RpiR TF HexR
2 HexR

Acidovorax avenae subsp. citrulli AAC00-1
2 HexR

Acidovorax sp. JS42
2 HexR

Comamonas testosteroni KF-1
4 HexR

Delftia acidovorans SPH-1
3 HexR

Polaromonas naphthalenivorans CJ2
4 HexR

Polaromonas sp. JS666
4 HexR

Rhodoferax ferrireducens DSM 15236
3 HexR

Verminephrobacter eiseniae EF01-2
3 HexR

Leptothrix cholodnii SP-6
Central carbohydrate metabolism
Rrf2 TF IscR
1 IscR

Acidovorax avenae subsp. citrulli AAC00-1
1 IscR

Acidovorax sp. JS42
1 IscR

Comamonas testosteroni KF-1
1 IscR

Delftia acidovorans SPH-1
1 IscR

Polaromonas naphthalenivorans CJ2
1 IscR

Polaromonas sp. JS666
1 IscR

Rhodoferax ferrireducens DSM 15236
1 IscR

Variovorax paradoxus S110
1 IscR

Verminephrobacter eiseniae EF01-2
1 IscR

Methylibium petroleiphilum PM1
1 IscR

Leptothrix cholodnii SP-6
Iron-sulfur cluster biogenesis
TF NsrR
2 NsrR

Acidovorax avenae subsp. citrulli AAC00-1
3 NsrR

Acidovorax sp. JS42
5 NsrR

Polaromonas naphthalenivorans CJ2
1 NsrR

Polaromonas sp. JS666
3 NsrR

Rhodoferax ferrireducens DSM 15236
Nitrosative stress response
TetR TF FadP
5 FadP

Acidovorax avenae subsp. citrulli AAC00-1
5 FadP

Acidovorax sp. JS42
3 FadP

Comamonas testosteroni KF-1
4 FadP

Delftia acidovorans SPH-1
4 FadP

Polaromonas naphthalenivorans CJ2
4 FadP

Polaromonas sp. JS666
6 FadP

Rhodoferax ferrireducens DSM 15236
4 FadP

Variovorax paradoxus S110
4 FadP

Verminephrobacter eiseniae EF01-2
4 FadP

Methylibium petroleiphilum PM1
3 FadP

Leptothrix cholodnii SP-6
Fatty acid degradation
TF LiuQ
2 LiuQ

Methylibium petroleiphilum PM1
2 LiuQ

Leptothrix cholodnii SP-6
Branched-chain amino acid degradation
TF PaaR
3 PaaR

Delftia acidovorans SPH-1
2 PaaR

Variovorax paradoxus S110
1 PaaR

Verminephrobacter eiseniae EF01-2
2 PaaR

Methylibium petroleiphilum PM1
3 PaaR

Leptothrix cholodnii SP-6
Phenylacetic acid degradation
RF00050 RNA FMN
1 FMN

Acidovorax sp. JS42
1 FMN

Comamonas testosteroni KF-1
1 FMN

Delftia acidovorans SPH-1
1 FMN

Variovorax paradoxus S110
Riboflavin biosynthesis
RF00059 RNA TPP
3 TPP

Acidovorax avenae subsp. citrulli AAC00-1
2 TPP

Acidovorax sp. JS42
3 TPP

Comamonas testosteroni KF-1
3 TPP

Delftia acidovorans SPH-1
1 TPP

Polaromonas naphthalenivorans CJ2
2 TPP

Polaromonas sp. JS666
4 TPP

Rhodoferax ferrireducens DSM 15236
2 TPP

Variovorax paradoxus S110
1 TPP

Verminephrobacter eiseniae EF01-2
2 TPP

Methylibium petroleiphilum PM1
2 TPP

Leptothrix cholodnii SP-6
Thiamine biosynthesis
RF01055 RNA MOCO_RNA_motif
RF01057 RNA SAH_riboswitch
2 SAH_riboswitch

Acidovorax avenae subsp. citrulli AAC00-1
2 SAH_riboswitch

Acidovorax sp. JS42
2 SAH_riboswitch

Comamonas testosteroni KF-1
2 SAH_riboswitch

Delftia acidovorans SPH-1
2 SAH_riboswitch

Polaromonas naphthalenivorans CJ2
2 SAH_riboswitch

Polaromonas sp. JS666
2 SAH_riboswitch

Rhodoferax ferrireducens DSM 15236
2 SAH_riboswitch

Variovorax paradoxus S110
1 SAH_riboswitch

Verminephrobacter eiseniae EF01-2
2 SAH_riboswitch

Methylibium petroleiphilum PM1
2 SAH_riboswitch

Leptothrix cholodnii SP-6
Methionine metabolism