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: homoserine methionine biosynthesis, methionine biosynthesis by sulfhydrylation
|Superclasses:||Biosynthesis → Amino Acids Biosynthesis → Individual Amino Acids Biosynthesis → Methionine Biosynthesis → Methionine De Novo Biosynthesis|
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 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 188.8.131.52) or a cobalamin-dependent enzyme (EC 184.108.40.206), 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 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 [Hwang02], 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 220.127.116.11, O-acetylhomoserine aminocarboxypropyltransferase is considered indicative of the presence of a direct sulfhydrylation pathway.
Superpathways: superpathway of methionine biosynthesis (by sulfhydrylation)
Subpathways: homocysteine biosynthesis
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
Hwang02: 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.
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
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
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
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
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, 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
Goulding97a: 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
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. 245–254.
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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