2.0 2015-09-08 17:50:22 -0600 2015-09-14 16:46:44 -0600 ECMDB24244 M2MDB006361 N5-methyl--tetrahydropteroyl tri-L-glutamate N5-methyl--tetrahydropteroyl tri-L-glutamate is an intermediate in L-methionine biosynthesis I and S-adenosyl-L-methionine cycle I in E.coli. In both pathways, it is a substrate for the enzyme cobalamin-dependent methionine synthase which catalyzes the reaction L-homocysteine + N5-methyl--tetrahydropteroyl tri-L-glutamate → L-methionine + tetrahydropteroyl tri-L-glutamate (BioCyc compound: CPD-1302). N5-Methyl--tetrahydropteroyl tri-L-glutamic acid C30H35N9O12 713.663 713.242711923 2-(4-{4-[(4-{[(2-amino-5-methyl-4-oxo-3,4,5,6,7,8-hexahydropteridin-6-yl)methyl]amino}phenyl)formamido]-4-carboxylatobutanamido}-4-carboxylatobutanamido)pentanedioate 2-(4-{4-[(4-{[(2-amino-5-methyl-4-oxo-3,6,7,8-tetrahydropteridin-6-yl)methyl]amino}phenyl)formamido]-4-carboxylatobutanamido}-4-carboxylatobutanamido)pentanedioate CN1C(CNC2=CC=C(C=C2)C(=O)NC(CCC(=O)NC(CCC(=O)NC(CCC([O-])=O)C([O-])=O)C([O-])=O)C([O-])=O)CNC2=C1C(=O)NC(N)=N2 InChI=1S/C30H39N9O12/c1-39-16(13-33-24-23(39)26(45)38-30(31)37-24)12-32-15-4-2-14(3-5-15)25(44)36-19(29(50)51)7-10-21(41)34-17(27(46)47)6-9-20(40)35-18(28(48)49)8-11-22(42)43/h2-5,16-19,32H,6-13H2,1H3,(H,34,41)(H,35,40)(H,36,44)(H,42,43)(H,46,47)(H,48,49)(H,50,51)(H4,31,33,37,38,45)/p-4 HVRNKDVLFAVCJF-UHFFFAOYSA-J logp 0.11 ALOGPS logs -2.92 ALOGPS solubility 9.48e-01 g/l ALOGPS logp -3.5 ChemAxon pka_strongest_acidic 2.68 ChemAxon pka_strongest_basic 3.14 ChemAxon iupac 2-(4-{4-[(4-{[(2-amino-5-methyl-4-oxo-3,4,5,6,7,8-hexahydropteridin-6-yl)methyl]amino}phenyl)formamido]-4-carboxylatobutanamido}-4-carboxylatobutanamido)pentanedioate ChemAxon average_mass 713.663 ChemAxon mono_mass 713.242711923 ChemAxon smiles CN1C(CNC2=CC=C(C=C2)C(=O)NC(CCC(=O)NC(CCC(=O)NC(CCC([O-])=O)C([O-])=O)C([O-])=O)C([O-])=O)CNC2=C1C(=O)NC(N)=N2 ChemAxon formula C30H35N9O12 ChemAxon inchi InChI=1S/C30H39N9O12/c1-39-16(13-33-24-23(39)26(45)38-30(31)37-24)12-32-15-4-2-14(3-5-15)25(44)36-19(29(50)51)7-10-21(41)34-17(27(46)47)6-9-20(40)35-18(28(48)49)8-11-22(42)43/h2-5,16-19,32H,6-13H2,1H3,(H,34,41)(H,35,40)(H,36,44)(H,42,43)(H,46,47)(H,48,49)(H,50,51)(H4,31,33,37,38,45)/p-4 ChemAxon inchikey HVRNKDVLFAVCJF-UHFFFAOYSA-J ChemAxon polar_surface_area 342.6 ChemAxon refractivity 226.41 ChemAxon polarizability 69.3 ChemAxon rotatable_bond_count 19 ChemAxon acceptor_count 17 ChemAxon donor_count 7 ChemAxon physiological_charge -4 ChemAxon formal_charge -4 ChemAxon methionine biosynthesis The 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. PW000814 Metabolic Specdb::MsMs 26249 Specdb::MsMs 26250 Specdb::MsMs 26251 Specdb::MsMs 32807 Specdb::MsMs 32808 Specdb::MsMs 32809 Methionine synthase P13009 METH_ECOLI metH http://ecmdb.ca/proteins/P13009.xml Homocysteine + N5-methyl--tetrahydropteroyl tri-L-glutamate + Homocysteine > tetrahydropteroyltri-L-glutamate + L-Methionine PW_R002892