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MetaCyc Pathway: L-methionine biosynthesis I
Traceable author statement to experimental supportInferred from experiment

Pathway diagram: L-methionine biosynthesis I

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 from L-homoserine, L-methionine biosynthesis by transsulfuration

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

Some taxa known to possess this pathway include : Escherichia coli K-12 substr. MG1655Inferred from experiment

Expected Taxonomic Range: Bacteria

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 can synthesize methionine using organic sulfur through transsulfuration of O-acylated homoserine with L-cysteine to form L-cystathionine. Cystathionine is then cleaved to L-homocysteine, which is methylated to methionine (this pathway) [Soda87].

Some bacteria, yeast and fungi can use a different route in which they directly assimilate inorganic sulfur by a sulfhydrylation (see L-methionine biosynthesis III). In that route hydrogen sulfide (H2S), the final product of microbial sulfate reduction (see MetaCyc pathway sulfate reduction I (assimilatory)) reacts with O-acylated homoserine, with replacement of the acetyl group by sulfide to form homocysteine (see L-homocysteine biosynthesis).

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].

The O-acyl group of homoserine is an acetyl group in fungi, yeast, and most Gram-positive bacteria (see L-methionine biosynthesis III) and a succinyl group in enteric bacteria and some other Gram-negative bacteria, such as Pseudomanas aeruginosa, and Pseudomonas putida (this pathway) ( [Vermeij99, Soda87, 1]).

While many organisms seem to contain both routes for methionine biosynthesis, in Escherichia coli and other enteric bacteria only the transsulfuration pathway is used (Greene, R.C. in [Neidhardt87] pp. 542-560). Published evidence for these pathways includes gene identification; complementation of known mutants; analysis of mutant phenotypes; and gene cloning, expression, and enzyme activity assays. The presence of EC, O-acetylhomoserine aminocarboxypropyltransferase was considered indicative of the presence of a direct sulfhydrylation pathway.

Superpathways: L-homoserine and L-methionine biosynthesis, superpathway of L-methionine biosynthesis (transsulfuration), superpathway of S-adenosyl-L-methionine biosynthesis, superpathway of L-lysine, L-threonine and L-methionine biosynthesis I, aspartate superpathway

Unification Links: EcoCyc:HOMOSER-METSYN-PWY

Cynthia J. Krieger on Wed Oct 15, 2003:
This pathway was formerly called methionine biosynthesis from homoserine.

Revised 07-May-2007 by Caspi R, SRI International
Last-Curated 22-Apr-2011 by Fulcher CA, SRI International


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.

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

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

Aitken03: Aitken SM, Kim DH, Kirsch JF (2003). "Escherichia coli cystathionine gamma-synthase does not obey ping-pong kinetics. Novel continuous assays for the elimination and substitution reactions." Biochemistry 42(38);11297-306. PMID: 14503880

Arifuzzaman06: Arifuzzaman M, Maeda M, Itoh A, Nishikata K, Takita C, Saito R, Ara T, Nakahigashi K, Huang HC, Hirai A, Tsuzuki K, Nakamura S, Altaf-Ul-Amin M, Oshima T, Baba T, Yamamoto N, Kawamura T, Ioka-Nakamichi T, Kitagawa M, Tomita M, Kanaya S, Wada C, Mori H (2006). "Large-scale identification of protein-protein interaction of Escherichia coli K-12." Genome Res 16(5);686-91. PMID: 16606699

Awano03: Awano N, Wada M, Kohdoh A, Oikawa T, Takagi H, Nakamori S (2003). "Effect of cysteine desulfhydrase gene disruption on L-cysteine overproduction in Escherichia coli." Appl Microbiol Biotechnol 62(2-3);239-43. PMID: 12883870

Awano05: Awano N, Wada M, Mori H, Nakamori S, Takagi H (2005). "Identification and functional analysis of Escherichia coli cysteine desulfhydrases." Appl Environ Microbiol 71(7);4149-52. PMID: 16000837

Bairoch93: 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, 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

Banerjee90a: Banerjee RV, Matthews RG (1990). "Cobalamin-dependent methionine synthase." FASEB J 1990;4(5);1450-9. PMID: 2407589

Belfaiza86: Belfaiza J, Parsot C, Martel A, de la Tour CB, Margarita D, Cohen GN, Saint-Girons I (1986). "Evolution in biosynthetic pathways: two enzymes catalyzing consecutive steps in methionine biosynthesis originate from a common ancestor and possess a similar regulatory region." Proc Natl Acad Sci U S A 83(4);867-71. PMID: 3513164

Bertoldi05: Bertoldi M, Cellini B, Laurents DV, Borri Voltattorni C (2005). "Folding pathway of the pyridoxal 5'-phosphate C-S lyase MalY from Escherichia coli." Biochem J 389(Pt 3);885-98. PMID: 15823094

Biran00: Biran D, Gur E, Gollan L, Ron EZ (2000). "Control of methionine biosynthesis in Escherichia coli by proteolysis." Mol Microbiol 37(6);1436-43. PMID: 10998174

Biran95: Biran D, Brot N, Weissbach H, Ron EZ (1995). "Heat shock-dependent transcriptional activation of the metA gene of Escherichia coli." J Bacteriol 177(5);1374-9. PMID: 7868613

Born99: Born TL, Blanchard JS (1999). "Enzyme-catalyzed acylation of homoserine: mechanistic characterization of the Escherichia coli metA-encoded homoserine transsuccinylase." Biochemistry 1999;38(43);14416-23. PMID: 10572016

Boysen10: Boysen A, Moller-Jensen J, Kallipolitis B, Valentin-Hansen P, Overgaard M (2010). "Translational regulation of gene expression by an anaerobically induced small non-coding RNA in Escherichia coli." J Biol Chem 285(14);10690-702. PMID: 20075074

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

Brzovic90: Brzovic P, Holbrook EL, Greene RC, Dunn MF (1990). "Reaction mechanism of Escherichia coli cystathionine gamma-synthase: direct evidence for a pyridoxamine derivative of vinylglyoxylate as a key intermediate in pyridoxal phosphate dependent gamma-elimination and gamma-replacement reactions." Biochemistry 1990;29(2);442-51. PMID: 2405904

Chen97a: 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

Chu85: Chu J, Shoeman R, Hart J, Coleman T, Mazaitis A, Kelker N, Brot N, Weissbach H (1985). "Cloning and expression of the metE gene in Escherichia coli." Arch Biochem Biophys 239(2);467-74. PMID: 2988449

Clausen00: Clausen T, Schlegel A, Peist R, Schneider E, Steegborn C, Chang YS, Haase A, Bourenkov GP, Bartunik HD, Boos W (2000). "X-ray structure of MalY from Escherichia coli: a pyridoxal 5'-phosphate-dependent enzyme acting as a modulator in mal gene expression." EMBO J 19(5);831-42. PMID: 10698925

Clausen96: Clausen T, Huber R, Laber B, Pohlenz HD, Messerschmidt A (1996). "Crystal structure of the pyridoxal-5'-phosphate dependent cystathionine beta-lyase from Escherichia coli at 1.83 A." J Mol Biol 262(2);202-24. PMID: 8831789

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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
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