2.02012-05-31 13:00:34 -06002015-09-13 12:56:08 -0600ECMDB00696M2MDB000175L-MethionineL-Methionine, in addition to being a substrate for protein synthesis, is an intermediate in transmethylation reactions, serving as the major methyl group donor, including the methyl groups for DNA and RNA intermediates. Methionine is a methyl acceptor for 5-methyltetrahydrofolate-homocysteine methyl transferase (methionine synthase), the only reaction that allows for the recycling of this form of folate, and is also a methyl acceptor for the catabolism of betaine. Methionine is also required for synthesis of cysteine. Methionine is accepted as the metabolic precursor for cysteine. Only the sulfur atom from methionine is transferred to cysteine; the carbon skeleton of cysteine is donated by serine. (PMID 16702340)(2S)-2-amino-4-(methylsulfanyl)butanoate(2S)-2-amino-4-(methylsulfanyl)butanoic acid(2S)-2-amino-4-(methylsulphanyl)butanoate(2S)-2-amino-4-(methylsulphanyl)butanoic acid(L)-methionine(S)-(+)-methionine(S)-2-amino-4-(methylthio)-Butanoate(S)-2-amino-4-(methylthio)-Butanoic acid(S)-2-Amino-4-(methylthio)butanoate(S)-2-Amino-4-(methylthio)butanoic acid(S)-2-amino-4-(methylthio)butyrate(S)-2-amino-4-(methylthio)butyric acid(S)-methionine2-Amino-4-(methylthio)butyrate2-Amino-4-(methylthio)butyric acid2-Amino-4-methylthiobutanoate2-Amino-4-methylthiobutanoic acida-amino-a-Aminobutyratea-amino-a-Aminobutyric acidA-Amino-g-methylmercaptobutyrateA-Amino-g-methylmercaptobutyric acidAcimethinAlpha-Amino-alpha-aminobutyrateAlpha-Amino-alpha-aminobutyric acidAlpha-Amino-gamma-methylmercaptobutyrateAlpha-Amino-gamma-methylmercaptobutyric acidCymethionG-Methylthio-a-aminobutyrateG-Methylthio-a-aminobutyric acidGamma-Methylthio-alpha-aminobutyrateGamma-Methylthio-alpha-aminobutyric acidH-Met-hH-Met-ohL(-)-amino-a-amino-a-AminobutyrateL(-)-amino-a-amino-a-Aminobutyric acidL(-)-Amino-alpha-amino-alpha-aminobutyrateL(-)-Amino-alpha-amino-alpha-aminobutyric acidL(-)-amino-g-MethylthiobutyrateL(-)-amino-g-Methylthiobutyric acidL(-)-Amino-gamma-methylthiobutyrateL(-)-Amino-gamma-methylthiobutyric acidL(-)-amino-α-amino-α-AminobutyrateL(-)-amino-α-amino-α-Aminobutyric acidL(-)-amino-γ-MethylthiobutyrateL(-)-amino-γ-Methylthiobutyric acidL-(-)-MethionineL-2-Amino-4-(methylthio)butyrateL-2-Amino-4-(methylthio)butyric acidL-2-amino-4-MethylthiobutyrateL-2-Amino-4-methylthiobutyric acidL-2-Amino-4methylthiobutyrateL-2-Amino-4methylthiobutyric acidL-a-amino-g-MethylmercaptobutyrateL-a-amino-g-Methylmercaptobutyric acidL-a-Amino-g-methylthiobutyrateL-a-Amino-g-methylthiobutyric acidL-alpha-Amino-gamma-methylmercaptobutyrateL-alpha-Amino-gamma-methylmercaptobutyric acidL-alpha-Amino-gamma-methylthiobutyrateL-alpha-Amino-gamma-methylthiobutyric acidL-g-methylthio-a-AminobutyrateL-g-methylthio-a-Aminobutyric acidL-gamma-Methylthio-alpha-aminobutyrateL-gamma-Methylthio-alpha-aminobutyric acidL-MethioninL-MethionineL-MethioninumL-α-amino-γ-MethylmercaptobutyrateL-α-amino-γ-Methylmercaptobutyric acidL-α-amino-γ-MethylthiobutyrateL-α-amino-γ-Methylthiobutyric acidL-γ-methylthio-α-AminobutyrateL-γ-methylthio-α-Aminobutyric acidLiquimethMMepronMETMethilaninMethionineMethioninumMetioninaNeo-methidinPoly-L-methioninePolymethionineS-MethionineS-Methyl-L-homocysteineToxin WARα-amino-α-Aminobutyrateα-amino-α-Aminobutyric acidα-amino-γ-Methylmercaptobutyrateα-amino-γ-Methylmercaptobutyric acidγ-methylthio-α-Aminobutyrateγ-methylthio-α-Aminobutyric acidC5H11NO2S149.211149.051049291(2S)-2-amino-4-(methylsulfanyl)butanoic acidL-methionine63-68-3CSCC[C@H](N)C(O)=OInChI=1S/C5H11NO2S/c1-9-3-2-4(6)5(7)8/h4H,2-3,6H2,1H3,(H,7,8)/t4-/m0/s1FFEARJCKVFRZRR-BYPYZUCNSA-NSolidCytosolExtra-organismPeriplasmlogp-1.85logs-0.80solubility2.39e+01 g/lmelting_point284 oClogp-2.2pka_strongest_acidic2.53pka_strongest_basic9.5iupac(2S)-2-amino-4-(methylsulfanyl)butanoic acidaverage_mass149.211mono_mass149.051049291smilesCSCC[C@H](N)C(O)=OformulaC5H11NO2SinchiInChI=1S/C5H11NO2S/c1-9-3-2-4(6)5(7)8/h4H,2-3,6H2,1H3,(H,7,8)/t4-/m0/s1inchikeyFFEARJCKVFRZRR-BYPYZUCNSA-Npolar_surface_area63.32refractivity37.59polarizability15.5rotatable_bond_count4acceptor_count3donor_count2physiological_charge0formal_charge0Cysteine and methionine metabolismec00270Selenoamino acid metabolismec00450Aminoacyl-tRNA biosynthesisec00970Porphyrin and chlorophyll metabolismec00860Biotin metabolismBiotin (vitamin H or vitamin B7) is the essential cofactor of biotin-dependent carboxylases, such as pyruvate carboxylase and acetyl-CoA carboxylase.In E. coli and many organisms, pimelate thioester is derived from malonyl-ACP. The pathway starts with a malonyl-[acp] interacting with S-adenosylmethionine through a biotin synthesis protein BioC resulting in a S-adenosylhomocysteine and a malonyl-[acp] methyl ester. The latter compound is then involved in the synthesis of a 3-ketoglutaryl-[acp] methyl ester through a 3-oxoacyl-[acyl-carrier-protein] synthase. The compound 3-ketoglutaryl-[acp] methyl ester is reduced by a NADPH mediated 3-oxoacyl-[acyl-carrier-protein] reductase resulting in a 3R-hydroxyglutaryl-[acp] methyl ester. This compound is then dehydrated through ad (3R)-hydroxymyristoyl-[acp] dehydratase producing a enoylglutaryl-[acp] methyl ester. This compound is then reduced through a NADPH mediated enoyl-acp-reductase [NADH] resulting in a glutaryl-[acp] methyl ester. This compound interacts with a malonyl-[acp] through a 3-oxoacyl-[acp] synthase 2 resulting in a 3-ketopimeloyl [acp] methyl ester. This compound is then reduced through a NADPH 3-oxoacyl [acp] reductase producing a 3-hydroxypimeloyl-[acp] methyl ester and then dehydrated by (3R)-hydroxymyristoyl-[acp] dehydratase to produce a enoylpimeloyl-[acp] methyl ester. This compound is then reduced by a NADPH dependent enoyl-[acp]reductase resulting in a pimeloyl-[acp] methyl ester. This compound then reacts with water through a carboxylesterase resulting in a pimeloyl-[acp] and a methanol. The pimeloyl-acp reacts with L-alanine through a 8-amino-7-oxononanoate synthase resulting in 8-amino-7-oxononanoate which in turn reacts with S-adenosylmethionine through a 7,8 diaminonanoate transaminase resulting in a S-adenosyl-4-methylthio-2-oxobutanoate and 7,8 diaminononanoate. The latter compound is then dephosphorylated through a dethiobiotin synthetase resulting in a dethiobiotin. This compound interacts with a sulfurated[sulfur carrier), a hydrogen ion and a S-adenosylmethionine through a biotin synthase to produce Biotin and releasing l-methionine and a 5-deoxyadenosine.
Biotin is then metabolized by a bifunctional protein resulting in pyrophosphate and Biotinyl-5-AMP which in turn reacts with the same protein (bifunctional protein birA resulting ina biotin caroxyl carrying protein.This product then enters the fatty acid biosynthesis.
PW000762ec00780MetabolicOne carbon pool by folateDihydrofolic acid, a product of the folate biosynthesis pathway, can be metabolized by multiple enzymes.
Dihydrofolic acid can be reduced by a NADP-driven dihydrofolate reductase resulting in a NADPH, hydrogen ion and folic acid.
Dihydrofolic acid can also be reduced by an NADPH-driven dihydrofolate reductase resulting in a NADP and a tetrahydrofolic acid. Folic acid can also produce a tetrahydrofolic acid through a NADPH-driven dihydrofolate reductase.
Dihydrofolic acid also interacts with 5-thymidylic acid through a thymidylate synthase resulting in the release of dUMP and 5,10-methylene-THF
Tetrahydrofolic acid can be converted into 5,10-methylene-THF through two different reversible reactions.
Tetrahydrofolic acid interacts with a S-Aminomethyldihydrolipoylprotein through a aminomethyltransferase resulting in the release of ammonia, a dihydrolipoylprotein and 5,10-Methylene-THF
Tetrahydrofolic acid interacts with L-serine through a glycine hydroxymethyltransferase resulting in a glycine, water and 5,10-Methylene-THF.
The compound 5,10-methylene-THF reacts with an NADPH dependent methylenetetrahydrofolate reductase [NAD(P)H] resulting in NADP and 5-Methyltetrahydrofolic acid. This compound interacts with homocysteine through a methionine synthase resulting in L-methionine and tetrahydrofolic acid.
Tetrahydrofolic acid can be metabolized into 10-formyltetrahydrofolate through 4 different enzymes:
1.- Tetrahydrofolic acid interacts with FAICAR through a phosphoribosylaminoimidazolecarboxamide formyltransferase resulting in a 1-(5'-Phosphoribosyl)-5-amino-4-imidazolecarboxamide and a 10-formyltetrahydrofolate
2.-Tetrahydrofolic acid interacts with 5'-Phosphoribosyl-N-formylglycinamide through a phosphoribosylglycinamide formyltransferase 2 resulting in a Glycineamideribotide and a 10-formyltetrahydrofolate
3.-Tetrahydrofolic acid interacts with Formic acid through a formyltetrahydrofolate hydrolase resulting in water and a 10-formyltetrahydrofolate
4.-Tetrahydrofolic acid interacts with N-formylmethionyl-tRNA(fMet) through a 10-formyltetrahydrofolate:L-methionyl-tRNA(fMet) N-formyltransferase resulting in a L-methionyl-tRNA(Met) and a 10-formyltetrahydrofolate
10-formyltetrahydrofolate can interact with a hydrogen ion through a bifunctional 5,10-methylene-tetrahydrofolate dehydrogenase resulting in water and
5,10-methenyltetrahydrofolic acid.
Tetrahydrofolic acid can be metabolized into 5,10-methenyltetrahydrofolic acid by reacting with a
5'-phosphoribosyl-a-N-formylglycineamidine through a phosphoribosylglycinamide formyltransferase 2 resulting in water, glycineamideribotide and 5,10-methenyltetrahydrofolic acid. The latter compound can either interact with water through an aminomethyltransferase resulting in a N5-Formyl-THF, or it can interact with a NADPH driven bifunctional 5,10-methylene-tetrahydrofolate dehydrogenase resulting in a NADP and 5,10-Methylene THF.
PW000773ec00670MetabolicThiamine metabolismec00730Lipoic acid metabolismLipoic acid metabolism starts with caprylic acid being introduced into the cytoplasm however no transporter has been identified yet.
Once caprylic acid is in the cytoplasm, it can either reacts with a holo-acp, through an ATP driven 2-acylglycerophosphoethanolamine acyltransferase / acyl-ACP synthetase resulting in pyrophosphate, AMP and octanoyl-[acp]. The latter compound can also be obtained from palmitate biosynthesis.
Octanoyl-acp interacts with a lipoyl-carrier protein L-lysine through a Octanoyltransferase resulting in a hydrogen ion, a holo-acyl-acp, and a protein N6-0octanoyl) lysine. The latter compound reacts with an S-adenosylmethionine, a sulfurated[sulfur carrier] and a reduced ferredoxin through a lipoate-protein ligase A, resulting in a 5-deoxyadenosine, a L-methionine, an unsulfurated [sulfur carrier], oxidized ferredoxin, and a Protein N6-(lipoyl) lysine.
Caprylic acid can also interact with ATP and a lipoyl-carrier protein-L-lysine through a lipoate-protein ligase A resulting in a amp, pyrophosphate, hydrogen ion, protein N6-(octanoyl)lysine. The latter compound reacts with an S-adenosylmethionine, a sulfurated[sulfur carrier] and a reduced ferredoxin through a lipoate-protein ligase A, resulting in a 5-deoxyadenosine, a L-methionine, an unsulfurated [sulfur carrier], oxidized ferredoxin, and a Protein N6-(lipoyl) lysine.
R-lipoic acid can be absorbed from the environment, as seen in studies by Morris TW. In this pathway the lipoyl-protein ligase LplA utilizes pre-existing lipoate that has been imported from outside the cell, and thus catalyzes a salvage pathway. Lipoic acid interacts with ATP and hydrogen ion through a lipoyl-protein ligase A, resulting in a pyrophosphate and a Lipoyl-AMP (lipoyl-adenylate). This compound then interacts with a lipoyl-carrier protein-L-lysine through a lipoate-protein ligase A resulting a AMP, a hydrogen ion
and a Protein N6-(lipoyl) lysine.
It has been suggested that the conversion of octanoylated-domains to lipoylated ones described in this pathway may be a type of a repair pathway, activated only if the other lipoate biosynthetic pathways are malfunctioning .
PW000770ec00785MetabolicMetabolic pathwayseco01100One Carbon Pool by Folate IDihydrofolic acid, a product of the folate biosynthesis pathway, can be metabolized by multiple enzymes.
Dihydrofolic acid can be reduced by a NADP-driven dihydrofolate reductase resulting in a NADPH, hydrogen ion and folic acid.
Dihydrofolic acid can also be reduced by an NADPH-driven dihydrofolate reductase resulting in a NADP and a tetrahydrofolic acid. Folic acid can also produce a tetrahydrofolic acid through a NADPH-driven dihydrofolate reductase.
Dihydrofolic acid also interacts with 5-thymidylic acid through a thymidylate synthase resulting in the release of dUMP and 5,10-methylene-THF
Tetrahydrofolic acid can be converted into 5,10-methylene-THF through two different reversible reactions.
Tetrahydrofolic acid interacts with a S-Aminomethyldihydrolipoylprotein through a aminomethyltransferase resulting in the release of ammonia, a dihydrolipoylprotein and 5,10-Methylene-THF
Tetrahydrofolic acid interacts with L-serine through a glycine hydroxymethyltransferase resulting in a glycine, water and 5,10-Methylene-THF.
The compound 5,10-methylene-THF reacts with an NADPH dependent methylenetetrahydrofolate reductase [NAD(P)H] resulting in NADP and 5-Methyltetrahydrofolic acid. This compound interacts with homocysteine through a methionine synthase resulting in L-methionine and tetrahydrofolic acid.
Tetrahydrofolic acid can be metabolized into 10-formyltetrahydrofolate through 4 different enzymes:
1.- Tetrahydrofolic acid interacts with FAICAR through a phosphoribosylaminoimidazolecarboxamide formyltransferase resulting in a 1-(5'-Phosphoribosyl)-5-amino-4-imidazolecarboxamide and a 10-formyltetrahydrofolate
2.-Tetrahydrofolic acid interacts with 5'-Phosphoribosyl-N-formylglycinamide through a phosphoribosylglycinamide formyltransferase 2 resulting in a Glycineamideribotide and a 10-formyltetrahydrofolate
3.-Tetrahydrofolic acid interacts with Formic acid through a formyltetrahydrofolate hydrolase resulting in water and a 10-formyltetrahydrofolate
4.-Tetrahydrofolic acid interacts with N-formylmethionyl-tRNA(fMet) through a 10-formyltetrahydrofolate:L-methionyl-tRNA(fMet) N-formyltransferase resulting in a L-methionyl-tRNA(Met) and a 10-formyltetrahydrofolate
10-formyltetrahydrofolate can interact with a hydrogen ion through a bifunctional 5,10-methylene-tetrahydrofolate dehydrogenase resulting in water and
5,10-methenyltetrahydrofolic acid.
Tetrahydrofolic acid can be metabolized into 5,10-methenyltetrahydrofolic acid by reacting with a
5'-phosphoribosyl-a-N-formylglycineamidine through a phosphoribosylglycinamide formyltransferase 2 resulting in water, glycineamideribotide and 5,10-methenyltetrahydrofolic acid. The latter compound can either interact with water through an aminomethyltransferase resulting in a N5-Formyl-THF, or it can interact with a NADPH driven bifunctional 5,10-methylene-tetrahydrofolate dehydrogenase resulting in a NADP and 5,10-Methylene THF.
PW001735MetabolicPorphyrin metabolismThe metabolism of porphyrin begins with with glutamic acid being processed by an ATP-driven glutamyl-tRNA synthetase by interacting with hydrogen ion and tRNA(Glu), resulting in amo, pyrophosphate and L-glutamyl-tRNA(Glu) Glutamic acid. Glutamic acid can be obtained as a result of L-glutamate metabolism pathway, glutamate / aspartate : H+ symporter GltP, glutamate:sodium symporter or a glutamate / aspartate ABC transporter .
L-glutamyl-tRNA(Glu) Glutamic acid interacts with a NADPH glutamyl-tRNA reductase resulting in a NADP, a tRNA(Glu) and a (S)-4-amino-5-oxopentanoate.
This compound interacts with a glutamate-1-semialdehyde aminotransferase resulting a 5-aminolevulinic acid. This compound interacts with a porphobilinogen synthase resulting in a hydrogen ion, water and porphobilinogen. The latter compound interacts with water resulting in hydroxymethylbilane synthase resulting in ammonium, and hydroxymethylbilane.
Hydroxymethylbilane can either be dehydrated to produce uroporphyrinogen I or interact with a uroporphyrinogen III synthase resulting in a water molecule and a uroporphyrinogen III.
Uroporphyrinogen I interacts with hydrogen ion through a uroporphyrinogen decarboxylase resulting in a carbon dioxide and a coproporphyrinogen I
Uroporphyrinogen III can be metabolized into precorrin by interacting with a S-adenosylmethionine through a siroheme synthase resulting in hydrogen ion, an s-adenosylhomocysteine and a precorrin-1. On the other hand, Uroporphyrinogen III interacts with hydrogen ion through a uroporphyrinogen decarboxylase resulting in a carbon dioxide and a Coproporphyrinogen III.
Precorrin-1 reacts with a S-adenosylmethionine through a siroheme synthase resulting in a S-adenosylhomocysteine and a Precorrin-2. The latter compound is processed by a NAD dependent uroporphyrin III C-methyltransferase [multifunctional] resulting in a NADH and a sirohydrochlorin. This compound then interacts with Fe 2+
uroporphyrin III C-methyltransferase [multifunctional] resulting in a hydrogen ion and a siroheme. The siroheme is then processed in sulfur metabolism pathway.
Uroporphyrinogen III can be processed in anaerobic or aerobic condition.
Anaerobic:
Uroporphyrinogen III interacts with an oxygen molecule, a hydrogen ion through a coproporphyrinogen III oxidase resulting in water, carbon dioxide and protoporphyrinogen IX. The latter compound then interacts with an 3 oxygen molecule through a protoporphyrinogen oxidase resulting in 3 hydrogen peroxide and a Protoporphyrin IX
Aerobic:
Uroporphyrinogen III reacts with S-adenosylmethionine through a coproporphyrinogen III dehydrogenase resulting in carbon dioxide, 5-deoxyadenosine, L-methionine and protoporphyrinogen IX. The latter compound interacts with a meanquinone through a protoporphyrinogen oxidase resulting in protoporphyrin IX.
The protoporphyrin IX interacts with Fe 2+ through a ferrochelatase resulting in a hydrogen ion and a ferroheme b. The ferroheme b can either be incorporated into the oxidative phosphorylation as a cofactor of the enzymes involved in that pathway or it can interact with hydrogen peroxide through a catalase HPII resulting in a heme D. Heme D can then be incorporated into the oxidative phosphyrlation pathway as a cofactor of the enzymes involved in that pathway. Ferroheme b can also interact with water and a farnesyl pyrophosphate through a heme O synthase resulting in a release of pyrophosphate and heme O. Heme O is then incorporated into the Oxidative phosphorylation pathway.
PW000936MetabolicS-adenosyl-L-methionine biosynthesisS-adenosyl-L-methionine biosynthesis(SAM) is synthesized in the cytosol of the cell from L-methionine and ATP. This reaction is catalyzed by methionine adenosyltransferase. L methione is taken up from the environment through a complex reaction coupled transport and then proceeds too synthesize the s adenosylmethionine through a adenosylmethionine synthase. The S-adenosylmethionine then interacts with a hydrogen ion through a adenosylmethionine decarboxylase resulting in a carbon dioxide and a S-adenosyl 3-methioninamine.This compound interacts with a putrescine through a spermidine synthase resulting in a spermidine, a hydrogen ion and a S-methyl-5'-thioadenosine. The latter compound is degraded by interacting with a water molecule through a 5' methylthioadenosine nucleosidase resulting in a adenine and a S-methylthioribose which is then release into the environmentPW000837Metabolicmethionine biosynthesisThe de novo biosynthesis of methionine is an energy-costly process involving inputs from several other pathways. The carbon skeleton of methionine is derived from aspartate. The sulfur is derived from cysteine which derives its sulfur from sulfate assimilation. The methyl group is derived from serine via one-carbon metabolism. Methionine is also converted to S-adenosyl-L-methionine, a methyl group donor, by the product of gene metK .
The synthesis starts with a product of the lysine biosynthesis pathway, L-aspartate-semialdehyde. This compound is dehydrogenated by a NADPH
aspartate kinase / homoserine dehydrogenase resulting in NADP and L-homoserine. Homoserine is activated by O-succinylation in a reaction catalyzed by MetA. The product O-succinyl-L-homoserine combines with cysteine to form cystathionine in a reaction catalyzed by MetB. Lyase cleavage of cystathionine by MetC forms homocysteine. This β-cystathionase activity can also be supplied by MalY as demonstrated in vivo by the ability of constitutive MalY expression to complement metC mutants auxotrophic for methionine . Homocysteine is subsequently methylated by either MetH or MetE to produce methionine. In E. coli MetH can function only in the presence of exogenously supplied vitamin B12 (cobalamin), which represses MetE expression. B12 is likely to be available in the gut. In the absence of exogenously supplied B12, MetE catalyzes this final step of de novo methionine biosynthesis.
L-methionine is then transferred into the periplasmic space through a leucine efflux transporter.
Under stressful conditions there is further regulation of the pathway enzymes. Under heat-shock conditions growth is slowed due to the thermal instability of MetA. Oxidative stress affects MetE which contains an oxidation-sensitive cysteine residue at position 645 near the active site. Oxidation of methionone itself can also occur although the cell contains methionine sufloxide reductases MsrA and MsrB to combat this. Weak organic acids also generate oxidative stress, with more complex effects. Sulfur limitation depletes homocysteine which serves as a coactivator for MetR activation of MetE expression.
Due to the absence of this pathway in mammals, some of the bacterial biosynthetic enzymes are potential drug targets. In addition, although methionine is used as a food additive and a medication, its industrial scale production in microorganisms has not yet been achieved due to the complexity and strong regulation of its biosynthetic pathway.PW000814MetabolicpreQ0 metabolismPreQ0 or 7-cyano-7-carbaguanine is biosynthesized by degrading GTP.
GTP first interacts with water through a GTP cyclohydrolase resulting in the release of a formate, a hydrogen ion and a 7,8-dihydroneopterin 3'-triphosphate. The latter compound then interacts with water through a 6-carboxy-5,6,7,8-tetrahydropterin synthase resulting in a acetaldehyde, triphosphate, 2 hydrogen ion and 6-carboxy-5,6,7,8-tetrahydropterin. The latter compound then reacts spontaneously with a hydrogen ion resulting in the release of a ammonium molecule and a 7-carboxy-7-deazaguanine. This compound then interacts with ATP and ammonium through 7-cyano-7-deazaguanine synthase resulting in the release of water, phosphate, ADP, hydrogen ion and a 7-cyano-7-carbaguanine.
The degradation of 7-cyano-7-deazaguanine can lead to produce a preQ1 or a queuine by reacting with 3 hydrogen ions and 2 NADPH through a 7-cyano-7-deazaguanine reductase. PreQ1 then interacts with a guanine 34 in tRNA through a tRNA-guanine transglycosylase resulting in a release of a guanine and a 7-aminomethyl-7-deazaguanosine 34 in tRNA. This nucleic acid then interacts with SAM through a S-adenosylmethionine tRNA ribosyltransferase-isomerase resulting in a release of a hydrogen ion, L-methionine, adenine and an epoxyqueuosinePW001893MetabolictRNA Charging 2This pathway groups together all E. coli tRNA charging reactions.PW000803MetabolictRNA chargingThis pathway groups together all E. coli tRNA charging reactions.PW000799Metabolictyrosine biosynthesisThe pathways of biosynthesis of phenylalaline and tyrosine are intimately connected. First step of both pathways is the conversion of chorismate to prephenate, the third step of both is the conversion of a ketoacid to the aminoacid through transamination. The two pathways differ only in the second step of their three-step reaction sequences: In the case of phenylalanine biosynthesi a dehydratase converts prephenate to phenylpyruvate(reaction occurs slowly in the absence of enzymic activity); in the case of tyrosine biosynthesis, a dehydrogenase converts prephenate to p-hydroxyphenylpyruvate. Also in both pathways the first two steps are catalyzed by two distinc active sites on a single protein. Thus the first step of each pathway can be catalyzed by two enzyme: those associated with both the phenylalanine specific dehydratase and the tyrosine specific dehydrogenase. Three enzymes those enconde by tyrB, aspC and ilvE are involved in catalyzing the third step of these pathways, all three can contribute to the synthesis of phenylalanine: only tyrB and aspC contribute to biosynthesis of tyrosinePW000806MetabolicThiamin diphosphate biosynthesisPW002028MetabolicThiazole Biosynthesis IThis pathway describes only the synthesis of the thiazole moiety of thiamin. Different variations of this pathway exist, this particular pathway describes the pathway that occurs in Escherichia coli K-12 and Salmonella enterica enterica serovar Typhimurium.
The biosynthesis of the thiazole moiety is complex. In Escherichia coli it involves six proteins, the products of the thiS, thiF, thiG, thiH, thiI, and iscS genes.
The process begins when IscS, a protein that is also involved in the biosynthesis of iron-sulfur clusters, catalyzes the transfer of a sulfur atom from cysteine to a ThiI sulfur-carrier protein, generating a an S-sulfanyl-[ThiI sulfur-carrier protein].
In a parallel route, the ThiF protein activates a ThiS sulfur-carrier protein by adenylation of its carboxy terminus, generating a carboxy-adenylated-[ThiS sulfur-carrier protein]. In a second reaction, which may also be catalyzed by ThiF, the sulfur from an S-sulfanyl-[ThiI sulfur-carrier protein] is transferred to ThiS, generating a thiocarboxy-[ThiS-Protein].
The final reaction of this pathway, which is catalyzed by the ThiG protein, requires three inputs: a thiocarboxy-[ThiS-Protein], 1-deoxy-D-xylulose 5-phosphate and 2-iminoacetate.
2-iminoacetate is formed in Escherichia coli from L-tyrosine by tyrosine lyase (ThiH), which forms a complex with ThiG.
For many years the products of this reaction was assumed to be 4-methyl-5-(β-hydroxyethyl)thiazole (thiazole). However, recent work performed with the thiazole synthase from Bacillus subtilis has shown that the actual product is the thiazole tautomer 2-[(2R,5Z)-(2-carboxy-4-methylthiazol-5(2H)-ylidene]ethyl phosphate. While in Bacillus a dedicated thiazole tautomerase converts this product into a different tautomer (2-(2-carboxy-4-methylthiazol-5-yl)ethyl phosphate), most of the proteobacteria lack the tautomerase. (EcoCyc)PW002041MetabolicLipoate Biosynthesis and Incorporation IThe biosynthesis of lipoate is unusual, and shares the same mechanism as the biosynthesis of biotin. The first enzyme in this pathway, lipoyl(octanoyl) transferase, transfers the octanoate moiety from octanoate-ACP molecules to specific lysyl residues in lipoate-dependent enzymes, resulting in octanylated domains, and regenerating the acyl-carrier protein in the process.
The next enzyme in the pathway, lipoyl synthase, catalyzes the conversion of the octanoyl side chain to an active lipoyl, generating a fully active lipoylated domain. The enzyme is an iron-sulfur protein that requires the presence of S-adenosyl-L-methionine. An electron which originates from the [4Fe-4S] cluster of the enzyme serves to split at least two molecules of AdoMet into a 5'-deoxyadenosyl radical and methionine. The radical then abstracts a hydrogen from a C-H bond of the octanoyl side chain, becoming 5'-adenosine in the process. The newly-formed unstable octanoyl radical then reacts directly with the Fe-S center of the enzyme. Two sulfur atoms from the center enter the structure of the octanoyl side chain, producing lipoyl, which dissociates from the enzyme along with excess iron, leaving it with a [2Fe-2S] center. Thus, in this unusual reaction, the iron-sulfur center of the enzyme is not just a catalytic accelerator, but also a substrate, donating the two sulfur atoms. It should be noted that although this process has been well documented in vitro, there is still a possibility that there exists another sulfur donor in vivo, and that the Fe-S center acts as sulfur donor only in the absence of this natural donor.
It has been suggested that the conversion of octanoylated-domains to lipoylated ones described in this pathway may be a type of a repair pathway, activated only if the other lipoate biosynthetic pathways are malfunctioning. (EcoCyc)PW002107MetabolicS-adenosyl-L-methionine cycleThe S-adenosyl-L-methionine cycle starts with S-adenosyl-L-methionine reacting with (a demethylated methyl donor ) dimethylglycine resulting in the release of a hydrogen ion, a betain (a methylated methyl donor) and a S-adenosyl-L-homocysteine. The s-adenosyl-L-homocysteine reacts with a water molecule through a S-adenosylhomocysteine nucleosidase resulting in the release of a adenine and a ribosyl-L-homocysteine. This compound in turn reacts with a s-ribosylhomocysteine lyase resulting in the release of a l-homocysteine and a autoinducer 2. The L-homocysteine reacts with a N5-methyl-tetrahydropteroyl tri-L-glutamate through a methionine synthase resulting in the release of a tetrahydropteroyl tri-L-glutamate and a methione. The methionine in turn reacts with a water molecule and ATP molecule through a methionine adenosyltransferase resulting in the release of a diphosphate, a phosphate and a s-adenosyl-L-methionine.PW002080Metabolicbiotin biosynthesis from 7-keto-8-aminopelargonatePWY0-1507methylphosphonate degradationPWY0-1533queuosine biosynthesisPWY-6700<i>S</i>-adenosyl-L-methionine cycle IPWY-6151thiazole biosynthesis I (E. coli)PWY-6892tRNA chargingTRNA-CHARGING-PWYlipoate biosynthesis and incorporation IIPWY0-1275formylTHF biosynthesis I1CMET2-PWYpreQ<sub>0</sub> biosynthesisPWY-6703methionine biosynthesis IHOMOSER-METSYN-PWY4-amino-2-methyl-5-diphosphomethylpyrimidine biosynthesisPWY-6890heme biosynthesis from uroporphyrinogen-III IIHEMESYN2-PWYsuperpathway of <i>S</i>-adenosyl-L-methionine biosynthesisSAM-PWYlipoate biosynthesis and incorporation IPWY0-501Specdb::CMs615Specdb::CMs616Specdb::CMs617Specdb::CMs1109Specdb::CMs1204Specdb::CMs2922Specdb::CMs30046Specdb::CMs30208Specdb::CMs30604Specdb::CMs30730Specdb::CMs30770Specdb::CMs31197Specdb::CMs31198Specdb::CMs37701Specdb::CMs170485Specdb::CMs1072495Specdb::CMs1072497Specdb::CMs1072499Specdb::NmrOneD1254Specdb::NmrOneD1484Specdb::NmrOneD4840Specdb::NmrOneD20602Specdb::NmrOneD20603Specdb::NmrOneD20604Specdb::NmrOneD20605Specdb::NmrOneD20606Specdb::NmrOneD20607Specdb::NmrOneD20608Specdb::NmrOneD20609Specdb::NmrOneD20610Specdb::NmrOneD20611Specdb::NmrOneD20612Specdb::NmrOneD20613Specdb::NmrOneD20614Specdb::NmrOneD20615Specdb::NmrOneD20616Specdb::NmrOneD20617Specdb::NmrOneD20618Specdb::NmrOneD20619Specdb::NmrOneD20620Specdb::NmrOneD20621Specdb::NmrOneD166452Specdb::MsMs969Specdb::MsMs970Specdb::MsMs971Specdb::MsMs4441Specdb::MsMs4442Specdb::MsMs4443Specdb::MsMs4444Specdb::MsMs4445Specdb::MsMs4446Specdb::MsMs4447Specdb::MsMs4448Specdb::MsMs4449Specdb::MsMs4450Specdb::MsMs4451Specdb::MsMs4452Specdb::MsMs4453Specdb::MsMs4454Specdb::MsMs4455Specdb::MsMs4456Specdb::MsMs4457Specdb::MsMs4458Specdb::MsMs4462Specdb::MsMs4463Specdb::MsMs179109Specdb::MsMs179110Specdb::NmrTwoD1031Specdb::NmrTwoD1430HMDB0069661375907C0007316811METMET_LFZWMETKeseler, I. M., Collado-Vides, J., Santos-Zavaleta, A., Peralta-Gil, M., Gama-Castro, S., Muniz-Rascado, L., Bonavides-Martinez, C., Paley, S., Krummenacker, M., Altman, T., Kaipa, P., Spaulding, A., Pacheco, J., Latendresse, M., Fulcher, C., Sarker, M., Shearer, A. G., Mackie, A., Paulsen, I., Gunsalus, R. P., Karp, P. D. (2011). "EcoCyc: a comprehensive database of Escherichia coli biology." Nucleic Acids Res 39:D583-D590.21097882Kanehisa, M., Goto, S., Sato, Y., Furumichi, M., Tanabe, M. (2012). "KEGG for integration and interpretation of large-scale molecular data sets." Nucleic Acids Res 40:D109-D114.22080510Vijayendran, C., Barsch, A., Friehs, K., Niehaus, K., Becker, A., Flaschel, E. (2008). "Perceiving molecular evolution processes in Escherichia coli by comprehensive metabolite and gene expression profiling." Genome Biol 9:R72.18402659van der Werf, M. J., Overkamp, K. M., Muilwijk, B., Coulier, L., Hankemeier, T. (2007). 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"Multiple high-throughput analyses monitor the response of E. coli to perturbations." Science 316:593-597.17379776Ball, R. O., Courtney-Martin, G., Pencharz, P. B. (2006). "The in vivo sparing of methionine by cysteine in sulfur amino acid requirements in animal models and adult humans." J Nutr 136:1682S-1693S.16702340Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4.19212411Shoemaker JD, Elliott WH: Automated screening of urine samples for carbohydrates, organic and amino acids after treatment with urease. 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Neurochem Res. 2004 Jan;29(1):319-24.14992292Kersemans V, Cornelissen B, Kersemans K, Bauwens M, Achten E, Dierckx RA, Mertens J, Slegers G: In vivo characterization of 123/125I-2-iodo-L-phenylalanine in an R1M rhabdomyosarcoma athymic mouse model as a potential tumor tracer for SPECT. J Nucl Med. 2005 Mar;46(3):532-9.15750170Alme B, Bremmelgaard A, Sjovall J, Thomassen P: Analysis of metabolic profiles of bile acids in urine using a lipophilic anion exchanger and computerized gas-liquid chromatorgaphy-mass spectrometry. J Lipid Res. 1977 May;18(3):339-62.864325Sardharwalla IB, Fowler B, Robins AJ, Komrower GM: Detection of heterozygotes for homocystinuria. Study of sulphur-containing amino acids in plasma and urine after L-methionine loading. 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World J Urol. 1999 Oct;17(5):308-15.10552150Harth G, Horwitz MA: Inhibition of Mycobacterium tuberculosis glutamine synthetase as a novel antibiotic strategy against tuberculosis: demonstration of efficacy in vivo. Infect Immun. 2003 Jan;71(1):456-64.12496196Takasu A, Shimosegawa T, Shimosegawa E, Hatazawa J, Kimura K, Fujita M, Koizumi M, Kanno I, Toyota T: 11C-methionine uptake to the pancreas and its secretion: a positron emission tomography study in humans. Pancreas. 1999 May;18(4):392-8.10231845van de Poll MC, Dejong CH, Soeters PB: Adequate range for sulfur-containing amino acids and biomarkers for their excess: lessons from enteral and parenteral nutrition. J Nutr. 2006 Jun;136(6 Suppl):1694S-1700S.16702341Garlick PJ: Toxicity of methionine in humans. J Nutr. 2006 Jun;136(6 Suppl):1722S-1725S.16702346Boy, Matthias; Klein, Daniela; Schroeder, Hartwig. Method for the production and recovery of methionine. PCT Int. Appl. (2005), 34 pp.http://hmdb.ca/system/metabolites/msds/000/000/615/original/HMDB00696.pdf?1358894682Methionyl-tRNA synthetaseP00959SYM_ECOLImetGhttp://ecmdb.ca/proteins/P00959.xmlAromatic-amino-acid aminotransferaseP04693TYRB_ECOLItyrBhttp://ecmdb.ca/proteins/P04693.xmlPeptide methionine sulfoxide reductase msrAP0A744MSRA_ECOLImsrAhttp://ecmdb.ca/proteins/P0A744.xmlPeptide methionine sulfoxide reductase msrBP0A746MSRB_ECOLImsrBhttp://ecmdb.ca/proteins/P0A746.xmlS-adenosylmethionine synthaseP0A817METK_ECOLImetKhttp://ecmdb.ca/proteins/P0A817.xmlPyruvate formate-lyase 1-activating enzymeP0A9N4PFLA_ECOLIpflAhttp://ecmdb.ca/proteins/P0A9N4.xmlAnaerobic ribonucleoside-triphosphate reductase-activating proteinP0A9N8NRDG_ECOLInrdGhttp://ecmdb.ca/proteins/P0A9N8.xmlThioredoxin-2P0AGG4THIO2_ECOLItrxChttp://ecmdb.ca/proteins/P0AGG4.xmlBiotin synthaseP12996BIOB_ECOLIbioBhttp://ecmdb.ca/proteins/P12996.xmlMethionine synthaseP13009METH_ECOLImetHhttp://ecmdb.ca/proteins/P13009.xmlBiotin sulfoxide reductaseP20099BISC_ECOLIbisChttp://ecmdb.ca/proteins/P20099.xml5-methyltetrahydropteroyltriglutamate--homocysteine methyltransferaseP25665METE_ECOLImetEhttp://ecmdb.ca/proteins/P25665.xmlD-methionine transport system permease protein metIP31547METI_ECOLImetIhttp://ecmdb.ca/proteins/P31547.xmlLipoate-protein ligase AP32099LPLA_ECOLIlplAhttp://ecmdb.ca/proteins/P32099.xmlOxygen-independent coproporphyrinogen-III oxidaseP32131HEMN_ECOLIhemNhttp://ecmdb.ca/proteins/P32131.xmlPyruvate formate-lyase 2-activating enzymeP32675PFLC_ECOLIpflChttp://ecmdb.ca/proteins/P32675.xmlOxygen-independent coproporphyrinogen-III oxidase-like protein yggWP52062YGGW_ECOLIyggWhttp://ecmdb.ca/proteins/P52062.xmlLipoyl synthaseP60716LIPA_ECOLIlipAhttp://ecmdb.ca/proteins/P60716.xmlPutative pyruvate formate-lyase 3-activating enzymeP75794PFLE_ECOLIybiYhttp://ecmdb.ca/proteins/P75794.xmlHomocysteine S-methyltransferaseQ47690MMUM_ECOLImmuMhttp://ecmdb.ca/proteins/Q47690.xmlMethionine import ATP-binding protein MetNP30750METN_ECOLImetNhttp://ecmdb.ca/proteins/P30750.xmlThiazole synthaseP30139THIG_ECOLIthiGhttp://ecmdb.ca/proteins/P30139.xmlDehydroglycine synthaseP30140THIH_ECOLIthiHhttp://ecmdb.ca/proteins/P30140.xmlD-methionine-binding lipoprotein metQP28635METQ_ECOLImetQhttp://ecmdb.ca/proteins/P28635.xmlPhosphomethylpyrimidine synthaseP30136THIC_ECOLIthiChttp://ecmdb.ca/proteins/P30136.xmlThioredoxin-1P0AA25THIO_ECOLItrxAhttp://ecmdb.ca/proteins/P0AA25.xmlpredicted acyltransferase with acyl-CoA N-acyltransferase domainP76112yncAhttp://ecmdb.ca/proteins/P76112.xmlS-adenosylmethionine:tRNA ribosyltransferase-isomeraseP0A7F9QUEA_ECOLIqueAhttp://ecmdb.ca/proteins/P0A7F9.xmlRibosomal RNA large subunit methyltransferase NP36979RLMN_ECOLIrlmNhttp://ecmdb.ca/proteins/P36979.xmltRNA-2-methylthio-N(6)-dimethylallyladenosine synthaseP0AEI1MIAB_ECOLImiaBhttp://ecmdb.ca/proteins/P0AEI1.xmlRibosomal protein S12 methylthiotransferase RimOP0AEI4RIMO_ECOLIrimOhttp://ecmdb.ca/proteins/P0AEI4.xmlD-methionine transport system permease protein metIP31547METI_ECOLImetIhttp://ecmdb.ca/proteins/P31547.xmlUncharacterized amino-acid ABC transporter ATP-binding protein yecCP37774YECC_ECOLIyecChttp://ecmdb.ca/proteins/P37774.xmlInner membrane amino-acid ABC transporter permease protein yecSP0AFT2YECS_ECOLIyecShttp://ecmdb.ca/proteins/P0AFT2.xmlMethionine import ATP-binding protein MetNP30750METN_ECOLImetNhttp://ecmdb.ca/proteins/P30750.xmlOuter membrane protein NP77747OMPN_ECOLIompNhttp://ecmdb.ca/proteins/P77747.xmlOuter membrane pore protein EP02932PHOE_ECOLIphoEhttp://ecmdb.ca/proteins/P02932.xmlOuter membrane protein FP02931OMPF_ECOLIompFhttp://ecmdb.ca/proteins/P02931.xmlD-methionine-binding lipoprotein metQP28635METQ_ECOLImetQhttp://ecmdb.ca/proteins/P28635.xmlOuter membrane protein CP06996OMPC_ECOLIompChttp://ecmdb.ca/proteins/P06996.xmlMethionine sulfoxide + Reduced Thioredoxin > Water + L-Methionine + Oxidized ThioredoxinAdenosine triphosphate + Water + L-Methionine > ADP + Hydrogen ion + L-Methionine + PhosphateRXN0-4522Adenosine triphosphate + Water + L-Methionine > ADP + Hydrogen ion + L-Methionine + PhosphateRXN0-45225-Methyltetrahydrofolic acid + L-Homocysteine <> Hydrogen ion + L-Methionine + Tetrahydrofolic acidR00946HOMOCYSMETB12-RXNL-Homocysteine + S-Methylmethionine > Hydrogen ion +2 L-MethionineS-Adenosylmethionine + L-Homocysteine + S-Methylmethionine <> S-Adenosylhomocysteine + Hydrogen ion + L-MethionineR00650HOMOCYSTEINE-S-METHYLTRANSFERASE-RXN[4Fe-4S] iron-sulfur cluster + 2 S-Adenosylmethionine + Hydrogen ion + NAD + octanoate (protein bound) > [2Fe-2S] iron-sulfur cluster +2 5'-Deoxyadenosine +2 Iron + lipoate (protein bound) +2 L-Methionine + NADH[2Fe-2S] iron-sulfur cluster + S-Adenosylmethionine + Dethiobiotin > [2Fe-1S] desulfurated iron-sulfur cluster + Biotin + 5'-Deoxyadenosine + Hydrogen ion + L-MethionineAdenosine triphosphate + L-Methionine + tRNA(Met) > Adenosine monophosphate + L-Methionyl-tRNA (Met) + PyrophosphateAdenosine triphosphate + Water + L-Methionine <> S-Adenosylmethionine + Phosphate + PyrophosphateR00177S-ADENMETSYN-RXN2 S-Adenosylmethionine + Coproporphyrin III <>2 Carbon dioxide +2 5'-Deoxyadenosine +2 L-Methionine + Protoporphyrinogen IXR06895S-Adenosylmethionine + NADPH + L-Tyrosine > p-Cresol + 5'-Deoxyadenosine + Dehydroglycine + Hydrogen ion + L-Methionine + NADPHydrogen peroxide + L-Methionine > Water + Methionine sulfoxidePhosphate + Pyrophosphate + S-Adenosylmethionine <> Adenosine triphosphate + L-Methionine + WaterR00177S-Adenosylmethionine + L-Homocysteine <> S-Adenosylhomocysteine + L-MethionineR00650HOMOCYSTEINE-S-METHYLTRANSFERASE-RXN5-Methyltetrahydrofolic acid + L-Homocysteine <> Tetrahydrofolic acid + L-MethionineR00946Dethiobiotin + Sulfur donor + 2 S-Adenosylmethionine + 2 e- + 2 Hydrogen ion <> Biotin +2 L-Methionine +2 5'-DeoxyadenosineR01078Adenosine triphosphate + L-Methionine + tRNA(Met) + tRNA(Met) <> Adenosine monophosphate + Pyrophosphate + L-Methionyl-tRNA + L-Methionyl-tRNAR036595-Methyltetrahydropteroyltri-L-glutamic acid + L-Homocysteine <> Tetrahydropteroyltri-L-glutamic acid + L-MethionineR044052-Oxo-4-methylthiobutanoic acid + L-Glutamate <> L-Methionine + alpha-KetoglutarateR07396Protein N6-(octanoyl)lysine + 2 Sulfur donor + 2 S-Adenosylmethionine + Protein N6-(octanoyl)lysine <> Protein N6-(lipoyl)lysine +2 L-Methionine +2 5'-Deoxyadenosine + Protein N6-(lipoyl)lysineR07767Octanoyl-[acp] + 2 Sulfur donor + 2 S-Adenosylmethionine <> Lipoyl-[acp] +2 L-Methionine +2 5'-DeoxyadenosineR07768L-Methionine + Hydrogen peroxide > L-methionine <i>S</i>-oxide + WaterRXN0-6721Hydrogen ion + α-D-ribose-1-methylphosphonate-5-phosphate + S-Adenosylmethionine > α-D-ribose-1,2-cyclic-phosphate-5-phosphate + methane + 5'-Deoxyadenosine + L-MethionineRXN0-6734L-Methionine + Acetyl-CoA N-α-acetyl-L-methionine + Coenzyme ARXN0-6948<i>S</i>-sulfanyl-[acceptor] + Dethiobiotin + S-Adenosylmethionine > an unsulfurated sulfur acceptor + Biotin + 5'-Deoxyadenosine + L-Methionine + Hydrogen ion2.8.1.6-RXNa protein with N-terminal methionine + Water > L-Methionine + Peptides3.4.11.18-RXNCoproporphyrinogen III + S-Adenosylmethionine > Protoporphyrinogen IX + Carbon dioxide + L-Methionine + 5'-DeoxyadenosineHEMN-RXNL-Homocysteine + 5-Methyltetrahydropteroyltri-L-glutamic acid > L-Methionine + tetrahydropteroyl tri-L-glutamateHOMOCYSMET-RXNL-Homocysteine + 5-Methyltetrahydrofolic acid L-Methionine + Tetrahydrofolic acidHOMOCYSMETB12-RXNL-Homocysteine + S-Adenosylmethionine Hydrogen ion + L-Methionine + S-AdenosylhomocysteineHOMOCYSTEINE-S-METHYLTRANSFERASE-RXNS-methyl-L-methionine + L-Homocysteine Hydrogen ion + L-MethionineMMUM-RXN5-Aminoimidazole ribonucleotide + S-Adenosylmethionine 4-Amino-2-methyl-5-phosphomethylpyrimidine + 5'-Deoxyadenosine + L-Methionine + Formic acid + carbon monoxide + Hydrogen ionPYRIMSYN1-RXNL-Methionine + a 2-oxo carboxylate 2-Oxo-4-methylthiobutanoic acid + a standard α amino acidR15-RXNS-Adenosylmethionine + Ribonuc-tri-P-reductases-inactive <> 5'-Deoxyadenosine + L-Methionine + Ribonuc-tri-P-reductases-activeRNTRACTIV-RXNL-Tyrosine + S-Adenosylmethionine + a reduced electron acceptor > Dehydroglycine + p-Cresol + 5'-Deoxyadenosine + L-Methionine + an oxidized electron acceptor + Hydrogen ionRXN-11319Water + Adenosine triphosphate + L-Methionine > Phosphate + ADP + L-Methionine + Hydrogen ionRXN0-4522Water + Adenosine triphosphate + L-Methionine > Phosphate + ADP + L-Methionine + Hydrogen ionRXN0-4522N-6-isopentyl adenosine-37 tRNA + S-Adenosylmethionine + <i>S</i>-sulfanyl-[acceptor] 2-methylthio-N-6-isopentyl adenosine-37 tRNA + S-Adenosylhomocysteine + L-Methionine + 5'-Deoxyadenosine + an unsulfurated sulfur acceptor + Hydrogen ionRXN0-50636-Carboxy-5,6,7,8-tetrahydropterin + S-Adenosylmethionine + Hydrogen ion > 7-carboxy-7-deazaguanine + 5'-Deoxyadenosine + L-Methionine + AmmoniaRXN0-6575gly-met + Water > Glycine + L-MethionineRXN0-6974methionine-alanine dipeptide + Water > L-Methionine + L-AlanineRXN0-6985Adenosine triphosphate + L-Methionine + Water > Phosphate + Pyrophosphate + S-AdenosylmethionineS-ADENMETSYN-RXNDethiobiotin + Hydrogen sulfide + 2 S-adenosyl-L-methionine > Biotin +2 L-Methionine +2 5'-DeoxyadenosineCoproporphyrinogen III + 2 S-adenosyl-L-methionine > Protoporphyrinogen IX +2 Carbon dioxide +2 L-Methionine +2 5'-DeoxyadenosineProtein N(6)-(octanoyl)lysine + 2 Hydrogen sulfide + 2 S-adenosyl-L-methionine > protein N(6)-(lipoyl)lysine +2 L-Methionine +2 5'-Deoxyadenosine5-methyltetrahydropteroyltri-L-glutamate + L-Homocysteine > tetrahydropteroyltri-L-glutamate + L-Methionine5-Methyltetrahydrofolic acid + L-Homocysteine > Tetrahydrofolic acid + L-MethionineAdenosine triphosphate + L-Methionine + Water > Inorganic phosphate + Pyrophosphate + S-adenosyl-L-methionineS-methyl-L-methionine + L-Homocysteine >2 L-MethionineL-Methionine + thioredoxin disulfide + Water > L-methionine (S)-S-oxide + thioredoxinL-Methionine + thioredoxin disulfide + Water > L-Methionine (R)-S-oxide + thioredoxinS-adenosyl-L-methionine + dihydroflavodoxin + [formate C-acetyltransferase]-glycine > 5'-Deoxyadenosine + L-Methionine + flavodoxin semiquinone + [formate C-acetyltransferase]-glycin-2-yl radicalS-adenosyl-L-methionine + 7-Aminomethyl-7-deazaguanosine > L-Methionine + Adenine + epoxyqueuosine2 S-adenosyl-L-methionine + adenine(2503) in 23S rRNA > S-Adenosylhomocysteine + L-Methionine + 5'-Deoxyadenosine + 2-methyladenine(2503) in 23S rRNAAdenosine triphosphate + L-Methionine + tRNA(Met) > Adenosine monophosphate + Pyrophosphate + L-methionyl-tRNA(Met)5-Aminoimidazole ribonucleotide + S-adenosyl-L-methionine > 4-Amino-2-methyl-5-phosphomethylpyrimidine + 5'-Deoxyadenosine + L-Methionine + Formic acid + COL-Tyrosine + S-adenosyl-L-methionine + reduced acceptor > 2-iminoacetate + p-Cresol + 5'-Deoxyadenosine + L-Methionine + acceptor +2 Hydrogen ionL-Methionine + a 2-oxo acid > 2-Oxo-4-methylthiobutanoic acid + an L-amino acidAcetyl-CoA + L-Methionine > CoA + N-Acetyl-L-methionine2 S-Adenosylmethionine <> S-Adenosylhomocysteine +2 L-Methionine + 5'-DeoxyadenosineR10645 2 S-Adenosylmethionine + Reduced acceptor <> S-Adenosylhomocysteine +2 L-Methionine + 5'-DeoxyadenosineR10652 L-Tyrosine + S-Adenosylmethionine + NADPH <> 2-iminoacetate + p-Cresol + 5'-Deoxyadenosine + L-Methionine + NADP + Hydrogen ionR10246 4-Amino-5-hydroxymethyl-2-methylpyrimidine + S-Adenosylmethionine <> 5-Aminoimidazole ribonucleotide + 4-Amino-2-methyl-5-phosphomethylpyrimidine + 5'-Deoxyadenosine + L-Methionine + Formic acid + COR03472Peptide-L-methionine + Thioredoxin disulfide + Water + L-Methionine <> Peptide-L-methionine (S)-S-oxide + Thioredoxin + L-methionine (S)-S-oxideR04120 Dethiobiotin + 2 S-adenosyl-L-methionine + 2 Hydrogen ion + a sulfurated [sulfur carrier] > Biotin +2 L-Methionine +2 5'-DeoxyadenosinePW_R002499Octanoyl-[acyl-carrier protein] + 2 a sulfur donor + 2 S-adenosyl-L-methionine > Lipoyl-ACP +2 L-Methionine + 5'-DeoxyadenosinePW_R002519Protein N6-(octanoyl)lysine + 2 a sulfur donor + 2 S-adenosyl-L-methionine > Protein N6-(lipoyl)lysine +2 L-Methionine +2 5'-DeoxyadenosinePW_R002522Protein N6-(octanoyl)lysine + 2 Reduced ferredoxin + 2 a sulfurated [sulfur carrier] + 2 S-adenosyl-L-methionine >2 L-Methionine +2 5'-Deoxyadenosine + Oxidized ferredoxin + Protein N6-(lipoyl)lysine + an unsulfurated [sulfur carrier]PW_R0035645-Methyltetrahydrofolic acid + Homocysteine + 5-Methyltetrahydrofolic acid + Homocysteine > Tetrahydrofolic acid + L-Methionine + Tetrahydrofolic acidPW_R002542Homocysteine + N5-methyl--tetrahydropteroyl tri-L-glutamate + Homocysteine > L-Methionine + tetrahydropteroyltri-L-glutamatePW_R002893L-Methionine + Adenosine triphosphate + Hydrogen ion + tRNA(Met) > Adenosine monophosphate + Pyrophosphate + L-methionyl-tRNA(Met)PW_R002841Homocysteine + N5-methyl--tetrahydropteroyl tri-L-glutamate + Homocysteine > tetrahydropteroyltri-L-glutamate + L-MethioninePW_R002892L-Methionine + Water + Adenosine triphosphate > Phosphate + PyrophosphatePW_R003074L-Methionine + Water + Adenosine triphosphate > Phosphate + Pyrophosphate + S-adenosyl-L-methioninePW_R003075S-adenosyl-L-methionine + Coproporphyrinogen III > 5'-Deoxyadenosine + L-Methionine + Carbon dioxide + Protoporphyrinogen IXPW_R003483L-Tyrosine + NADPH + S-adenosyl-L-methionine + L-Tyrosine + NADPH > Hydrogen ion + NADP + L-Methionine + 5'-Deoxyadenosine + p-Cresol + 2-iminoacetatePW_R0051747-aminomethyl-7-deazaguanosine34 in tRNA + S-adenosyl-L-methionine > Hydrogen ion + L-Methionine + Adenine + epoxyqueuosinePW_R005185L-Methionine + Adenosine triphosphate + Water > Adenosine diphosphate + Phosphate + Hydrogen ion + L-Methionine + ADPPW_RCT000111L-Methionine + Adenosine triphosphate + Water > Adenosine diphosphate + Phosphate + Hydrogen ion + L-Methionine + ADPPW_RCT000111L-Methionine + Adenosine triphosphate + Water > Adenosine diphosphate + Pyrophosphate + Hydrogen ion + L-Methionine + ADPPW_RCT000125L-Methionine + Adenosine triphosphate + Water > Adenosine diphosphate + Pyrophosphate + Hydrogen ion + L-Methionine + ADPPW_RCT000125Homocysteine + S-Methylmethionine <>2 L-Methionine + Hydrogen ionPW_R0058745-Aminoimidazole ribonucleotide + S-adenosyl-L-methionine >3 Hydrogen ion + CO + Formic acid + L-Methionine + 5'-Deoxyadenosine + 4-amino-2-methyl-5-phosphomethylpyrimidinePW_R005931L-Tyrosine + S-adenosyl-L-methionine + NADPH > Dehydroglycine + 4-Methylcatechol + 5'-Deoxyadenosine + L-Methionine + NADP + Hydrogen ionPW_R005962a [lipoyl-carrier protein] N6-octanoyl-L-lysine + 2 S-adenosyl-L-methionine + 2 a sulfurated [sulfur carrier] + 2 Reduced ferredoxin > Protein N6-(lipoyl)lysine +2 5'-Deoxyadenosine +2 L-Methionine +2 an unsulfurated [sulfur carrier] +2 Oxidized ferredoxinPW_R0061382 S-Adenosylmethionine + Coproporphyrin III <>2 Carbon dioxide +2 5'-Deoxyadenosine +2 L-Methionine + Protoporphyrinogen IXDethiobiotin + Sulfur donor + 2 S-Adenosylmethionine + 2 e- + 2 Hydrogen ion <> Biotin +2 L-Methionine +2 5'-DeoxyadenosineAdenosine triphosphate + Water + L-Methionine <> S-Adenosylmethionine + Phosphate + Pyrophosphate2 S-Adenosylmethionine + Reduced acceptor <> S-Adenosylhomocysteine +2 L-Methionine +5 5'-Deoxyadenosine5 5-Methyltetrahydrofolic acid + L-Homocysteine <> Hydrogen ion + L-Methionine + Tetrahydrofolic acidAdenosine triphosphate + L-Methionine + tRNA(Met) <> Adenosine monophosphate + Pyrophosphate + L-Methionyl-tRNA2 S-Adenosylmethionine <> S-Adenosylhomocysteine +2 L-Methionine +5 5'-Deoxyadenosine4 4-Amino-5-hydroxymethyl-2-methylpyrimidine + S-Adenosylmethionine <>5 5-Aminoimidazole ribonucleotide +4 4-Amino-2-methyl-5-phosphomethylpyrimidine +5 5'-Deoxyadenosine + L-Methionine + Formic acid + COPeptide-L-methionine + Thioredoxin disulfide + Water + L-Methionine <> Peptide-L-methionine (S)-S-oxide + Thioredoxin + L-methionine (S)-S-oxide2 S-Adenosylmethionine + Coproporphyrin III <>2 Carbon dioxide +2 5'-Deoxyadenosine +2 L-Methionine + Protoporphyrinogen IXDethiobiotin + Sulfur donor + 2 S-Adenosylmethionine + 2 e- + 2 Hydrogen ion <> Biotin +2 L-Methionine +2 5'-Deoxyadenosine2 S-Adenosylmethionine + Reduced acceptor <> S-Adenosylhomocysteine +2 L-Methionine +5 5'-Deoxyadenosine2 S-Adenosylmethionine + Coproporphyrin III <>2 Carbon dioxide +2 5'-Deoxyadenosine +2 L-Methionine + Protoporphyrinogen IX5 5-Methyltetrahydrofolic acid + L-Homocysteine <> Hydrogen ion + L-Methionine + Tetrahydrofolic acidProtein N6-(octanoyl)lysine + 2 Sulfur donor + 2 S-Adenosylmethionine <> Protein N6-(lipoyl)lysine +2 L-Methionine +2 5'-DeoxyadenosineAdenosine triphosphate + L-Methionine + tRNA(Met) <> Adenosine monophosphate + Pyrophosphate + L-Methionyl-tRNA4 4-Amino-5-hydroxymethyl-2-methylpyrimidine + S-Adenosylmethionine <>5 5-Aminoimidazole ribonucleotide +4 4-Amino-2-methyl-5-phosphomethylpyrimidine +5 5'-Deoxyadenosine + L-Methionine + Formic acid + COPeptide-L-methionine + Thioredoxin disulfide + Water + L-Methionine <> Peptide-L-methionine (S)-S-oxide + Thioredoxin + L-methionine (S)-S-oxideGutnick minimal complete medium (4.7 g/L KH2PO4; 13.5 g/L K2HPO4; 1 g/L K2SO4; 0.1 g/L MgSO4-7H2O; 10 mM NH4Cl) with 4 g/L glucoseShake flask and filter culture145.0uM0.037 oCK12 NCM3722Mid-Log Phase5800000Bennett, B. D., Kimball, E. H., Gao, M., Osterhout, R., Van Dien, S. J., Rabinowitz, J. D. (2009). "Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli." Nat Chem Biol 5:593-599.19561621Gutnick minimal complete medium (4.7 g/L KH2PO4; 13.5 g/L K2HPO4; 1 g/L K2SO4; 0.1 g/L MgSO4-7H2O; 10 mM NH4Cl) with 4 g/L glycerolShake flask and filter culture129.0uM0.037 oCK12 NCM3722Mid-Log Phase5160000Bennett, B. D., Kimball, E. H., Gao, M., Osterhout, R., Van Dien, S. J., Rabinowitz, J. D. (2009). "Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli." Nat Chem Biol 5:593-599.19561621Gutnick minimal complete medium (4.7 g/L KH2PO4; 13.5 g/L K2HPO4; 1 g/L K2SO4; 0.1 g/L MgSO4-7H2O; 10 mM NH4Cl) with 4 g/L acetateShake flask and filter culture65.9uM0.037 oCK12 NCM3722Mid-Log Phase2636000Bennett, B. D., Kimball, E. H., Gao, M., Osterhout, R., Van Dien, S. J., Rabinowitz, J. D. (2009). "Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli." Nat Chem Biol 5:593-599.1956162148 mM Na2HPO4, 22 mM KH2PO4, 10 mM NaCl, 45 mM (NH4)2SO4, supplemented with 1 mM MgSO4, 1 mg/l thiamine·HCl, 5.6 mg/l CaCl2, 8 mg/l FeCl3, 1 mg/l MnCl2·4H2O, 1.7 mg/l ZnCl2, 0.43 mg/l CuCl2·2H2O, 0.6 mg/l CoCl2·2H2O and 0.6 mg/l Na2MoO4·2H2O. 4 g/L GlucoBioreactor, pH controlled, O2 and CO2 controlled, dilution rate: 0.2/h30.3uM0.037 oCBW25113Stationary Phase, glucose limited1212000Ishii, N., Nakahigashi, K., Baba, T., Robert, M., Soga, T., Kanai, A., Hirasawa, T., Naba, M., Hirai, K., Hoque, A., Ho, P. Y., Kakazu, Y., Sugawara, K., Igarashi, S., Harada, S., Masuda, T., Sugiyama, N., Togashi, T., Hasegawa, M., Takai, Y., Yugi, K., Arakawa, K., Iwata, N., Toya, Y., Nakayama, Y., Nishioka, T., Shimizu, K., Mori, H., Tomita, M. (2007). "Multiple high-throughput analyses monitor the response of E. coli to perturbations." Science 316:593-597.17379776Luria-Bertani (LB) mediaShake flask58.4uMtrue7.037 oCBL21 DE3Stationary phase cultures (overnight culture)23360028000Lin, Z., Johnson, L. C., Weissbach, H., Brot, N., Lively, M. O., Lowther, W. T. (2007). "Free methionine-(R)-sulfoxide reductase from Escherichia coli reveals a new GAF domain function." Proc Natl Acad Sci U S A 104:9597-9602.17535911Luria-Bertani (LB) mediaShake flask42.57uMtrue4.7537 oCBL21 DE3Stationary phase cultures (overnight culture)17026719000Lin, Z., Johnson, L. C., Weissbach, H., Brot, N., Lively, M. O., Lowther, W. T. (2007). "Free methionine-(R)-sulfoxide reductase from Escherichia coli reveals a new GAF domain function." Proc Natl Acad Sci U S A 104:9597-9602.17535911