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Pathway Description
Isoleucine Biosynthesis
Escherichia coli
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2015-03-23
Last Updated: 2025-09-06
Isoleucine biosynthesis begins with L-threonine from the threonine biosynthesis pathway. L-threonine interacts with threonine dehydratase biosynthetic releasing water, a hydrogen ion and (2Z)-2-aminobut-2-enoate. The latter is isomerized into a 2-iminobutanoate which interacts with water and a hydrogen ion spontaneously, resulting in the release of ammonium and 2-ketobutyric acid. 2-ketobutyric acid reacts with pyruvic acid and hydrogen ions through an acetohydroxybutanoate synthase / acetolactate synthase 2 resulting in carbon dioxide and (S)-2-Aceto-2-hydroxybutanoic acid. (S)-2-Aceto-2-hydroxybutanoic acid is reduced by an NADPH driven acetohydroxy acid isomeroreductase releasing NADP and acetohydroxy acid isomeroreductase. The latter compound is dehydrated by a dihydroxy acid dehydratase resulting in 3-methyl-2-oxovaleric acid. This compound reacts in a reversible reaction with L-glutamic acid through a Branched-chain-amino-acid aminotransferase resulting in oxoglutaric acid and L-isoleucine.
L-isoleucine can also be transported into the cytoplasm through two different methods: a branched chain amino acid ABC transporter or a branched chain amino acid transporter BrnQy.
References
Isoleucine Biosynthesis References
Bell SC, Turner JM, Collins J, Gray TR: Patterns of microbial threonine catabolism: a survey. Biochem J. 1972 Apr;127(3):77P.
Pubmed: 5076220
Bell SC, Turner JM: Bacterial catabolism of threonine. Threonine degradation initiated by l-threonine hydrolyase (deaminating) in a species of Corynebacterium. Biochem J. 1977 Jun 15;164(3):579-87.
Pubmed: 16743051
Calhoun DH, Rimerman RA, Hatfield GW: Threonine deaminase from Escherichia coli. I. Purification and properties. J Biol Chem. 1973 May 25;248(10):3511-6.
Pubmed: 4573981
Gollop N, Damri B, Barak Z, Chipman DM: Kinetics and mechanism of acetohydroxy acid synthase isozyme III from Escherichia coli. Biochemistry. 1989 Jul 25;28(15):6310-7.
Pubmed: 2675968
Grimminger H, Umbarger HE: Acetohydroxy acid synthase I of Escherichia coli: purification and properties. J Bacteriol. 1979 Feb;137(2):846-53.
Pubmed: 370104
Komatsubara S, Murata K, Kisumi M, Chibata I: Threonine degradation by Serratia marcescens. J Bacteriol. 1978 Aug;135(2):318-23.
Pubmed: 355220
Lee-Peng FC, Hermodson MA, Kohlhaw GB: Transaminase B from Escherichia coli: quaternary structure, amino-terminal sequence, substrate specificity, and absence of a separate valine-alpha-ketoglutarate activity. J Bacteriol. 1979 Aug;139(2):339-45.
Pubmed: 378964
MYERS JW: Dihydroxy acid dehydrase: an enzyme involved in the biosynthesis of isoleucine and valine. J Biol Chem. 1961 May;236:1414-8.
Pubmed: 13727223
Ratzkin B, Arfin S, Umbarger HE: Isoleucine and valine metabolism in Escherichia coli. 18. Induction of acetohydroxy acid isomeroreductase. J Bacteriol. 1972 Oct;112(1):131-41.
Pubmed: 4562389
UMBARGER HE, BROWN B: Threonine deamination in Escherichia coli. II. Evidence for two L-threonine deaminases. J Bacteriol. 1957 Jan;73(1):105-12.
Pubmed: 13405870
Lopes JM, Lawther RP: Physical identification of an internal promoter, ilvAp, in the distal portion of the ilvGMEDA operon. Gene. 1989;76(2):255-69. doi: 10.1016/0378-1119(89)90166-2.
Pubmed: 2473940
Cox JL, Cox BJ, Fidanza V, Calhoun DH: The complete nucleotide sequence of the ilvGMEDA cluster of Escherichia coli K-12. Gene. 1987;56(2-3):185-98. doi: 10.1016/0378-1119(87)90136-3.
Pubmed: 3315862
Lawther RP, Wek RC, Lopes JM, Pereira R, Taillon BE, Hatfield GW: The complete nucleotide sequence of the ilvGMEDA operon of Escherichia coli K-12. Nucleic Acids Res. 1987 Mar 11;15(5):2137-55. doi: 10.1093/nar/15.5.2137.
Pubmed: 3550695
Kuramitsu S, Ogawa T, Ogawa H, Kagamiyama H: Branched-chain amino acid aminotransferase of Escherichia coli: nucleotide sequence of the ilvE gene and the deduced amino acid sequence. J Biochem. 1985 Apr;97(4):993-9. doi: 10.1093/oxfordjournals.jbchem.a135176.
Pubmed: 3897211
Pagel JM, Winkelman JW, Adams CW, Hatfield GW: DNA topology-mediated regulation of transcription initiation from the tandem promoters of the ilvGMEDA operon of Escherichia coli. J Mol Biol. 1992 Apr 20;224(4):919-35. doi: 10.1016/0022-2836(92)90460-2.
Pubmed: 1569580
Wek RC, Hauser CA, Hatfield GW: The nucleotide sequence of the ilvBN operon of Escherichia coli: sequence homologies of the acetohydroxy acid synthase isozymes. Nucleic Acids Res. 1985 Jun 11;13(11):3995-4010. doi: 10.1093/nar/13.11.3995.
Pubmed: 2989782
Friden P, Donegan J, Mullen J, Tsui P, Freundlich M, Eoyang L, Weber R, Silverman PM: The ilvB locus of Escherichia coli K-12 is an operon encoding both subunits of acetohydroxyacid synthase I. Nucleic Acids Res. 1985 Jun 11;13(11):3979-93. doi: 10.1093/nar/13.11.3979.
Pubmed: 2989781
Burland V, Plunkett G 3rd, Daniels DL, Blattner FR: DNA sequence and analysis of 136 kilobases of the Escherichia coli genome: organizational symmetry around the origin of replication. Genomics. 1993 Jun;16(3):551-61. doi: 10.1006/geno.1993.1230.
Pubmed: 7686882
Squires CH, De Felice M, Devereux J, Calvo JM: Molecular structure of ilvIH and its evolutionary relationship to ilvG in Escherichia coli K12. Nucleic Acids Res. 1983 Aug 11;11(15):5299-313. doi: 10.1093/nar/11.15.5299.
Pubmed: 6308579
Yura T, Mori H, Nagai H, Nagata T, Ishihama A, Fujita N, Isono K, Mizobuchi K, Nakata A: Systematic sequencing of the Escherichia coli genome: analysis of the 0-2.4 min region. Nucleic Acids Res. 1992 Jul 11;20(13):3305-8. doi: 10.1093/nar/20.13.3305.
Pubmed: 1630901
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
Wek RC, Hatfield GW: Nucleotide sequence and in vivo expression of the ilvY and ilvC genes in Escherichia coli K12. Transcription from divergent overlapping promoters. J Biol Chem. 1986 Feb 15;261(5):2441-50.
Pubmed: 3003115
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
Brown OR, Smyk-Randall E, Draczynska-Lusiak B, Fee JA: Dihydroxy-acid dehydratase, a [4Fe-4S] cluster-containing enzyme in Escherichia coli: effects of intracellular superoxide dismutase on its inactivation by oxidant stress. Arch Biochem Biophys. 1995 May 10;319(1):10-22. doi: 10.1006/abbi.1995.1262.
Pubmed: 7771772
Lawther RP, Nichols B, Zurawski G, Hatfield GW: The nucleotide sequence preceding and including the beginning of the ilvE gene of the ilvGEDA operon of Escherichia coli K12. Nucleic Acids Res. 1979 Dec 20;7(8):2289-301. doi: 10.1093/nar/7.8.2289.
Pubmed: 392469
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 SMP0000838
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