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MetaCyc Pathway: L-methionine biosynthesis III
Traceable author statement to experimental support

Enzyme View:

Pathway diagram: L-methionine biosynthesis III

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Synonyms: L-methionine biosynthesis by sulfhydrylation

Superclasses: BiosynthesisAmino Acids BiosynthesisProteinogenic Amino Acids BiosynthesisL-methionine BiosynthesisL-methionine De Novo Biosynthesis

Some taxa known to possess this pathway include : Corynebacterium glutamicum, Leptospira meyeri, Saccharomyces cerevisiae, [Brevibacterium] flavum

Expected Taxonomic Range: Bacteria , Fungi

L-methionine (met) is an essential amino acid and is required for a number of important cellular functions, including the initiation of protein synthesis, the methylation of DNA, rRNA and xenobiotics, and the biosynthesis of cysteine, phospholipids and polyamines.

Some bacteria, yeast and fungi can directly assimilate inorganic sulfur for the biosynthesis of sulfur-containing amino acids. Such a direct sulfhydrylation pathway for the biosynthesis of methionine is shown here. L-homoserine is biosynthesized from L-aspartate as shown in L-homoserine biosynthesis.

L-homoserine is activated through esterification to form the O-acetyl ester. Hydrogen sulfide (H2S), the final product of microbial sulfate reduction (see sulfate reduction I (assimilatory)) reacts with O-acetylated homoserine, with replacement of the acetyl group by sulfide to form L-homocysteine.

L-homocysteine is methylated to L-methionine via either a cobalamin-independent enzyme ( EC or a cobalamin-dependent enzyme ( EC, depending upon the species or growth conditions [Thomas97, Ruckert03].

Another route of microbial methionine biosynthesis involves the use of organic sulfur through transsulfuration of O-acylated homoserine with L-cysteine to form L-cystathionine, which is then cleaved to L-homocysteine, followed by methylation to L-methionine (see MetaCyc pathway L-methionine biosynthesis I) (reviewed in [Soda87]).

The O-acyl group of homoserine is an acetyl group in fungi, yeast, and most Gram-positive bacteria, and a succinyl group in enteric bacteria and some other Gram-negative bacteria, such as Pseudomonas aeruginosa and Pseudomonas putida ( [Vermeij99, Soda87, Thomas97]).

Organisms for which there is evidence for the existence of a direct sulfhydrylation pathway for methionine biosynthesis include Saccharomyces cerevisiae (reviewed in [Thomas97]), the spirochete Leptospira myeri [Belfaiza98, Picardeau03], Bacillus subtilis [Auger02], [Brevibacterium] flavum [Ozaki82, Shiio81], Corynebacterium glutamicum [Hwang02a], Pseudomonas aeruginosa [Vermeij99], and Pseudomonas putida [Vermeij99]. In these organisms, there is also evidence for the transsulfuration pathway, and the use of one pathway may predominate over the other. In Escherichia coli and other enteric bacteria only the transsulfuration pathway is used (Greene, R.C. in [Neidhardt87] pp. 542-560).

The presence of EC, O-acetylhomoserine aminocarboxypropyltransferase is considered indicative of the presence of a direct sulfhydrylation pathway.

Superpathways: superpathway of L-methionine biosynthesis (by sulfhydrylation)

Subpathways: L-homocysteine biosynthesis

Created 28-Jul-1998 by Ying HC, SRI International


Auger02: Auger S, Yuen WH, Danchin A, Martin-Verstraete I (2002). "The metIC operon involved in methionine biosynthesis in Bacillus subtilis is controlled by transcription antitermination." Microbiology 148(Pt 2);507-18. PMID: 11832514

Belfaiza98: Belfaiza J, Martel A, Margarita D, Saint Girons I (1998). "Direct sulfhydrylation for methionine biosynthesis in Leptospira meyeri." J Bacteriol 180(2);250-5. PMID: 9440513

Hwang02a: Hwang BJ, Yeom HJ, Kim Y, Lee HS (2002). "Corynebacterium glutamicum utilizes both transsulfuration and direct sulfhydrylation pathways for methionine biosynthesis." J Bacteriol 184(5);1277-86. PMID: 11844756

Neidhardt87: Neidhardt FC, Ingraham J, Low KB, Magasanik B, Schaechter M, Umbarger HE "Escherichia coli and Salmonella typhimurium, Cellular and Molecular Biology, Volumes 1 & 2." Microbiology, Washington, D.C., 1987.

Ozaki82: Ozaki H, Shiio I (1982). "Methionine biosynthesis in Brevibacterium flavum: properties and essential role of O-acetylhomoserine sulfhydrylase." J Biochem (Tokyo) 91(4);1163-71. PMID: 7096282

Picardeau03: Picardeau M, Bauby H, Saint Girons I (2003). "Genetic evidence for the existence of two pathways for the biosynthesis of methionine in the Leptospira spp." FEMS Microbiol Lett 225(2);257-62. PMID: 12951250

Ruckert03: Ruckert C, Puhler A, Kalinowski J (2003). "Genome-wide analysis of the L-methionine biosynthetic pathway in Corynebacterium glutamicum by targeted gene deletion and homologous complementation." J Biotechnol 104(1-3);213-28. PMID: 12948640

Shiio81: Shiio I, Ozaki H (1981). "Feedback inhibition by methionine and S-adenosylmethionine, and desensitization of homoserine O-acetyltransferase in Brevibacterium flavum." J Biochem (Tokyo) 89(5);1493-500. PMID: 7275950

Soda87: Soda K (1987). "Microbial sulfur amino acids: an overview." Methods Enzymol 143;453-9. PMID: 3309561

Thomas97: Thomas D, Surdin-Kerjan Y (1997). "Metabolism of sulfur amino acids in Saccharomyces cerevisiae." Microbiol Mol Biol Rev 61(4);503-32. PMID: 9409150

Vermeij99: Vermeij P, Kertesz MA (1999). "Pathways of assimilative sulfur metabolism in Pseudomonas putida." J Bacteriol 181(18);5833-7. PMID: 10482527

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Bairoch93a: Bairoch A, Boeckmann B (1993). "The SWISS-PROT protein sequence data bank, recent developments." Nucleic Acids Res. 21:3093-3096. PMID: 8332529

Banerjee89: Banerjee RV, Johnston NL, Sobeski JK, Datta P, Matthews RG (1989). "Cloning and sequence analysis of the Escherichia coli metH gene encoding cobalamin-dependent methionine synthase and isolation of a tryptic fragment containing the cobalamin-binding domain." J Biol Chem 1989;264(23);13888-95. PMID: 2668277

Banerjee90: Banerjee RV, Matthews RG (1990). "Cobalamin-dependent methionine synthase." FASEB J 1990;4(5);1450-9. PMID: 2407589

Banerjee90a: Banerjee RV, Frasca V, Ballou DP, Matthews RG (1990). "Participation of cob(I) alamin in the reaction catalyzed by methionine synthase from Escherichia coli: a steady-state and rapid reaction kinetic analysis." Biochemistry 1990;29(50);11101-9. PMID: 2271698

Baroni86: Baroni M, Livian S, Martegani E, Alberghina L (1986). "Molecular cloning and regulation of the expression of the MET2 gene of Saccharomyces cerevisiae." Gene 46(1);71-8. PMID: 3542717

Bourhy97: Bourhy P, Martel A, Margarita D, Saint Girons I, Belfaiza J (1997). "Homoserine O-acetyltransferase, involved in the Leptospira meyeri methionine biosynthetic pathway, is not feedback inhibited." J Bacteriol 179(13);4396-8. PMID: 9209059

BRENDA14: BRENDA team (2014). Imported from BRENDA version existing on Aug 2014.

Chen97: Chen LH, Liu ML, Hwang HY, Chen LS, Korenberg J, Shane B (1997). "Human methionine synthase. cDNA cloning, gene localization, and expression." J Biol Chem 272(6);3628-34. PMID: 9013615

Csaikl86: Csaikl U, Csaikl F (1986). "Molecular cloning and characterization of the MET6 gene of Saccharomyces cerevisiae." Gene 46(2-3);207-14. PMID: 3542720

DAndrea87: D'Andrea R, Surdin-Kerjan Y, Pure G, Cherest H (1987). "Molecular genetics of met 17 and met 25 mutants of Saccharomyces cerevisiae: intragenic complementation between mutations of a single structural gene." Mol Gen Genet 207(1);165-70. PMID: 3299001

Eichel95: Eichel J, Gonzalez JC, Hotze M, Matthews RG, Schroder J (1995). "Vitamin-B12-independent methionine synthase from a higher plant (Catharanthus roseus). Molecular characterization, regulation, heterologous expression, and enzyme properties." Eur J Biochem 230(3);1053-8. PMID: 7601135

Fleischhacker07: Fleischhacker AS, Matthews RG (2007). "Ligand trans influence governs conformation in cobalamin-dependent methionine synthase." Biochemistry 46(43);12382-92. PMID: 17924667

Frasca88: Frasca V, Banerjee RV, Dunham WR, Sands RH, Matthews RG (1988). "Cobalamin-dependent methionine synthase from Escherichia coli B: electron paramagnetic resonance spectra of the inactive form and the active methylated form of the enzyme." Biochemistry 27(22);8458-65. PMID: 2853966

Gakiere99: Gakiere B, Job D, Douce R, Ravanel S "Characterization of the cDNA and Gene for a Cytosolic Cobalamin-Independent Methionine Synthase in Arabidopsis thaliana (Accession No. U97200). (PGR99-115)." Plant Physiol. (1999), 120, 1206.

Goulding97: Goulding CW, Matthews RG (1997). "Cobalamin-dependent methionine synthase from Escherichia coli: involvement of zinc in homocysteine activation." Biochemistry 1997;36(50);15749-57. PMID: 9398304

Goulding97a: Goulding CW, Postigo D, Matthews RG (1997). "Cobalamin-dependent methionine synthase is a modular protein with distinct regions for binding homocysteine, methyltetrahydrofolate, cobalamin, and adenosylmethionine." Biochemistry 36(26);8082-91. PMID: 9201956

Grobbelaar58: Grobbelaar, N, Steward FC (1958). "O-acetylhomoserine in Pisum." Nature 182(4646);1358-9. PMID: 13600320

Grundy02: Grundy,F.J., Henkin,T.M. (2002). "Synthesis of serine, glycine, cysteine, and methionine." in Sonenshein,A.L., Hoch,J.A. and Losick,R. (eds), Bacillus subtilis and its Relatives: From Genes to Cells. American Society for Microbiology, Washington, DC, pp. 245254.

Guest64: Guest JR, Friedman S, Foster MA, Tejerina G, Woods DD (1964). "Transfer of the methyl group from N5-methyltetrahydrofolates to homocysteine in Escherichia coli." Biochem J 92(3);497-504. PMID: 5319972

Hacham03: Hacham Y, Gophna U, Amir R (2003). "In vivo analysis of various substrates utilized by cystathionine gamma-synthase and O-acetylhomoserine sulfhydrylase in methionine biosynthesis." Mol Biol Evol 20(9);1513-20. PMID: 12832650

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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by Pathway Tools version 19.5 (software by SRI International) on Mon May 2, 2016, biocyc14.