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Pathway Description
Methionine Biosynthesis
Escherichia coli 536
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2024-12-25
Last Updated: 2025-07-16
This pathway shows the biosynthesis of methionine, which is an energy-costly process. Lysine biosynthesis produces L-Aspartate-semialdehyde, which later on is catalyzed to L-homoserine by bifunctional aspartokinase (also named homoserine dehydrogenase) 1 and 2. Homoserine is then activated by O-succinylation to form O-succinyl-L-homoserine via homoserine O-succinyltransferase (metA). Combining with L-cysteine, O-succinyl-L-homoserine form L-cystathionine and succinic acid by cystathionine gamma-synthase (metB). Cleavage of L-cystathionine by cystathionine beta-lyase (metC) or Protein MalY(as ) generates two small molecules: homocysteine and 2-aminoprop-2-enoate. Methionine synthase(MetH) or 5-methyltetrahydropteroyltriglutamate--homocysteine methyltransferase(MetE) will catalyzehomocysteine to form the final product: methionine. In E.coli, MetH can only function with existence of cobalamin (Vitamin B12), which can be available in the guy; without cobalamin, MetE will not be repressed so that it will catalyze the methionine. Methionine can be transported out of cell (into periplasmic space) by leucine efflux transporter.
References
Methionine Biosynthesis References
Duclos B, Cortay JC, Bleicher F, Ron EZ, Richaud C, Saint Girons I, Cozzone AJ: Nucleotide sequence of the metA gene encoding homoserine trans-succinylase in Escherichia coli. Nucleic Acids Res. 1989 Apr 11;17(7):2856. doi: 10.1093/nar/17.7.2856.
Pubmed: 2654885
Michaeli S, Mevarech M, Ron EZ: Regulatory region of the metA gene of Escherichia coli K-12. J Bacteriol. 1984 Dec;160(3):1158-62.
Pubmed: 6094503
Born TL, Blanchard JS: Enzyme-catalyzed acylation of homoserine: mechanistic characterization of the Escherichia coli metA-encoded homoserine transsuccinylase. Biochemistry. 1999 Oct 26;38(43):14416-23. doi: 10.1021/bi991710o.
Pubmed: 10572016
Duchange N, Zakin MM, Ferrara P, Saint-Girons I, Park I, Tran SV, Py MC, Cohen GN: Structure of the metJBLF cluster in Escherichia coli K12. Sequence of the metB structural gene and of the 5'- and 3'-flanking regions of the metBL operon. J Biol Chem. 1983 Dec 25;258(24):14868-71.
Pubmed: 6361020
Plunkett G 3rd, Burland V, Daniels DL, Blattner FR: Analysis of the Escherichia coli genome. III. DNA sequence of the region from 87.2 to 89.2 minutes. Nucleic Acids Res. 1993 Jul 25;21(15):3391-8. doi: 10.1093/nar/21.15.3391.
Pubmed: 8346018
Blattner FR, Plunkett G 3rd, Bloch CA, Perna NT, Burland V, Riley M, Collado-Vides J, Glasner JD, Rode CK, Mayhew GF, Gregor J, Davis NW, Kirkpatrick HA, Goeden MA, Rose DJ, Mau B, Shao Y: The complete genome sequence of Escherichia coli K-12. Science. 1997 Sep 5;277(5331):1453-62. doi: 10.1126/science.277.5331.1453.
Pubmed: 9278503
Belfaiza J, Parsot C, Martel A, de la Tour CB, Margarita D, Cohen GN, Saint-Girons I: 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. 1986 Feb;83(4):867-71. doi: 10.1073/pnas.83.4.867.
Pubmed: 3513164
Hayashi K, Morooka N, Yamamoto Y, Fujita K, Isono K, Choi S, Ohtsubo E, Baba T, Wanner BL, Mori H, Horiuchi T: Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110. Mol Syst Biol. 2006;2:2006.0007. doi: 10.1038/msb4100049. Epub 2006 Feb 21.
Pubmed: 16738553
Reidl J, Boos W: The malX malY operon of Escherichia coli encodes a novel enzyme II of the phosphotransferase system recognizing glucose and maltose and an enzyme abolishing the endogenous induction of the maltose system. J Bacteriol. 1991 Aug;173(15):4862-76. doi: 10.1128/jb.173.15.4862-4876.1991.
Pubmed: 1856179
Aiba H, Baba T, Hayashi K, Inada T, Isono K, Itoh T, Kasai H, Kashimoto K, Kimura S, Kitakawa M, Kitagawa M, Makino K, Miki T, Mizobuchi K, Mori H, Mori T, Motomura K, Nakade S, Nakamura Y, Nashimoto H, Nishio Y, Oshima T, Saito N, Sampei G, Horiuchi T, et al.: A 570-kb DNA sequence of the Escherichia coli K-12 genome corresponding to the 28.0-40.1 min region on the linkage map. DNA Res. 1996 Dec 31;3(6):363-77. doi: 10.1093/dnares/3.6.363.
Pubmed: 9097039
Zakin MM, Duchange N, Ferrara P, Cohen GN: Nucleotide sequence of the metL gene of Escherichia coli. Its product, the bifunctional aspartokinase ii-homoserine dehydrogenase II, and the bifunctional product of the thrA gene, aspartokinase I-homoserine dehydrogenase I, derive from a common ancestor. J Biol Chem. 1983 Mar 10;258(5):3028-31.
Pubmed: 6298218
Katinka M, Cossart P, Sibilli L, Saint-Girons I, Chalvignac MA, Le Bras G, Cohen GN, Yaniv M: Nucleotide sequence of the thrA gene of Escherichia coli. Proc Natl Acad Sci U S A. 1980 Oct;77(10):5730-3. doi: 10.1073/pnas.77.10.5730.
Pubmed: 7003595
Cossart P, Katinka M, Yaniv M, Saint Girons I, Cohen GN: Construction and expression of a hybrid plasmid containing the Escherichia coli thrA and thrB genes. Mol Gen Genet. 1979 Aug;175(1):39-44. doi: 10.1007/bf00267853.
Pubmed: 390305
Thanbichler M, Neuhierl B, Bock A: S-methylmethionine metabolism in Escherichia coli. J Bacteriol. 1999 Jan;181(2):662-5.
Pubmed: 9882684
Old IG, Margarita D, Glass RE, Saint Girons I: Nucleotide sequence of the metH gene of Escherichia coli K-12 and comparison with that of Salmonella typhimurium LT2. Gene. 1990 Mar 1;87(1):15-21. doi: 10.1016/0378-1119(90)90490-i.
Pubmed: 2185137
Banerjee RV, Johnston NL, Sobeski JK, Datta P, Matthews RG: 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 Aug 15;264(23):13888-95.
Pubmed: 2668277
Drummond JT, Loo RR, Matthews RG: Electrospray mass spectrometric analysis of the domains of a large enzyme: observation of the occupied cobalamin-binding domain and redefinition of the carboxyl terminus of methionine synthase. Biochemistry. 1993 Sep 14;32(36):9282-9. doi: 10.1021/bi00087a004.
Pubmed: 8369296
Gonzalez JC, Banerjee RV, Huang S, Sumner JS, Matthews RG: Comparison of cobalamin-independent and cobalamin-dependent methionine synthases from Escherichia coli: two solutions to the same chemical problem. Biochemistry. 1992 Jul 7;31(26):6045-56. doi: 10.1021/bi00141a013.
Pubmed: 1339288
Daniels DL, Plunkett G 3rd, Burland V, Blattner FR: Analysis of the Escherichia coli genome: DNA sequence of the region from 84.5 to 86.5 minutes. Science. 1992 Aug 7;257(5071):771-8. doi: 10.1126/science.1379743.
Pubmed: 1379743
This pathway was propagated using PathWhiz -
Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
Propagated from SMP0000834
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