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Escherichia coli K-12 substr. MG1655 Pathway: homoserine and methionine biosynthesis

If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Locations of Mapped Genes:

Genetic Regulation Schematic: ?

Superclasses: Biosynthesis Amino Acids Biosynthesis Individual Amino Acids Biosynthesis Methionine Biosynthesis Methionine De Novo Biosynthesis

The synthesis of lysine, methionine and threonine share the first two reactions of the three pathways, the reactions converting L-aspartate to L-aspartate semialdehyde. There are three aspartate kinases, three isozymes coded for by the lysC, metL and thrA genes, one specific for synthesis of each end product amino acid. Each of the three aspartate kinase isozymes is regulated by its corresponding end product amino acid. The second reaction is also shared, catalyzed by aspartate semialdehyde dehydrogenase. In this case a single enzyme coded by the asd gene serves all three pathways. The third reaction is shared by the methionine and threonine pathways. Homoserine dehydrogenase, part of multifunctional enzymes, is coded by the metL and thrA genes. Therefore, independent regulation of the three pathways is possible. The synthesis of methionine is linked to intermediary metabolism through pyruvate and succinyl CoA. Also the amino acid cysteine is linked with methionine through O-succinyl homserine. Also, the last reaction of the methionine pathway lies at the point of convergence of two major biosynthetic pathways, that for homocysteine and for methyl group transfer via tetrahydrofolate derivatives. [Banerjee90, Smith71]

Superpathways: superpathway of S-adenosyl-L-methionine biosynthesis

Subpathways: homoserine biosynthesis , methionine biosynthesis I

Created 02-Feb-1994 by Riley M , Marine Biological Laboratory


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

Smith71: Smith DA (1971). "S-amino acid metabolism and its regulation in Escherichia coli and Salmonella typhimurium." Adv Genet 1971;16;141-65. PMID: 4947102

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

Alvarez04: Alvarez E, Ramon F, Magan C, Diez E (2004). "L-cystine inhibits aspartate-beta-semialdehyde dehydrogenase by covalently binding to the essential 135Cys of the enzyme." Biochim Biophys Acta 1696(1);23-9. PMID: 14726201

Angeles90: Angeles TS, Viola RE (1990). "The kinetic mechanisms of the bifunctional enzyme aspartokinase-homoserine dehydrogenase I from Escherichia coli." Arch Biochem Biophys 283(1);96-101. PMID: 2241177

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

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

Bearer78: Bearer CF, Neet KE (1978). "Threonine inhibition of the aspartokinase--homoserine dehydrogenase I of Escherichia coli. A slow transient and cooperativity of inhibition of the aspartokinase activity." Biochemistry 1978;17(17);3523-30. PMID: 28752

Belfaiza84: Belfaiza J, Fazel A, Muller K, Cohen GN (1984). "E. coli aspartokinase II-homoserine dehydrogenase II polypeptide chain has a triglobular structure." Biochem Biophys Res Commun 123(1);16-20. PMID: 6383377

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

Biellmann80: Biellmann JF, Eid P, Hirth C, Jornvall H (1980). "Aspartate-beta-semialdehyde dehydrogenase from Escherichia coli. Purification and general properties." Eur J Biochem 1980;104(1);53-8. PMID: 6102909

Biellmann80a: Biellmann JF, Eid P, Hirth C (1980). "Affinity labeling of the Escherichia coli aspartate-beta-semialdehyde dehydrogenase with an alkylating coenzyme analogue. Half-site reactivity and competition with the substrate alkylating analogue." Eur J Biochem 1980;104(1);65-9. PMID: 6102911

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

Boy72: Boy E, Patte JC (1972). "Multivalent repression of aspartic semialdehyde dehydrogenase in Escherichia coli K-12." J Bacteriol 112(1);84-92. PMID: 4404058

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

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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
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