Escherichia coli K-12 substr. MG1655 Pathway: L-isoleucine biosynthesis I (from threonine)
Inferred from experiment

Pathway diagram: L-isoleucine biosynthesis I (from threonine)

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

Locations of Mapped Genes:

Schematic showing all replicons, marked with selected genes

Genetic Regulation Schematic

Genetic regulation schematic for L-isoleucine biosynthesis I (from threonine)

Superclasses: BiosynthesisAmino Acids BiosynthesisProteinogenic Amino Acids BiosynthesisL-isoleucine Biosynthesis

The pathway of isoleucine biosynthesis from threonine is a five-step pathway that shares its last four steps with the pathway of valine biosynthesis. These entwined pathways are part of the superpathway of branched amino acid biosynthesis, that generates not only isoleucine and valine, but also leucine.

As a consequence of having several of its component enzymes involved in the synthesis of three different amino acids, the pathway of isoleucine biosynthesis is subject to regulation by all three amino acids. The first enzyme in the pathway, L-threonine deaminase, is downregulated by isoleucine and leucine, but is upregulated by valine. The following pathway step, catalyzed by acetohydroxybutanoate synthases (AHAS) I and III, is inhibited by all three amino acids. This apparent paradox of valine stimulation of step one followed by valine inhibition of step two is a product of the preference of AHAS III for processing of the isoleucine precursor 2-oxobutanoate rather than the valine precursor pyruvate. When valine is abundant in the cell, both AHAS enzymes are inhibited, blocking valine production and potentially disrupting isoleucine synthesis as well. However, the stimulation of L-threonine deaminase generates a substantial pool of 2-oxobutanoate. Combined with the high affinity of AHAS III for this compound, this allows the isoleucine synthesis to continue despite inhibition caused by the parallel valine synthesis pathway.

Enteric bacteria such as Escherichia coli K-12 substr. MG1655 and Salmonella enterica enterica serovar Typhimurium have been shown to possess two types of threonine dehydratases - a catabolic enzyme, which is induced by threonine, and a consistitutively- produced biosynthetic enzyme [Umbarger57]. Both enzymes convert threonine to 2-oxobutanoate, but differ in their regulation and expression.

Biosynthetic threonine dehydratases were also described in several soil bacteria [Bell77]. A survey of 75 soil isolates capable of growth on L-threonine revealed a group of three organisms that possessed substantial L-threonine dehydratase activity, to the exclusion of any other threonine-catabolyzing enzyme [Bell72]. The group consisted of Corynebacterium sp. F5 and two Brevibacterium isolates. The enzyme from Corynebacterium sp. F5 was partially purified, and was found to be of the biosynthetic type on the criteria that its formation was consitutive, it was susceptible to inhibition by L-isoleucine, L-valine protected against denaturation and was a positive effector and antagonist of isoleucine, and neither AMP nor ADP acted as effectors [Bell77]. Interestingly, even though the enzyme was of the biosynthetic type, the researchers found that much of the threonine in these organisms was converted to propanoate in a catabolic pathway identical to that described in L-threonine degradation I. Thus, the biosynthetic enzyme was recruited to a catabolic pathway.

A biosynthetic threonine dehydratase was also reported in Serratia marcescens [Komatsubara78].

Citations: [Neidhardt96 ]

Superpathways: superpathway of L-threonine metabolism, superpathway of branched amino acid biosynthesis

Unification Links: EcoCyc:ILEUSYN-PWY

Created 02-Feb-1994 by Riley M, Marine Biological Laboratory
Last-Curated 08-Nov-2007 by Shearer A, SRI International


Bell72: Bell SC, Turner JM, Collins J, Gray TR (1972). "Patterns of microbial threonine catabolism: a survey." Biochem J 127(3);77P. PMID: 5076220

Bell77: Bell SC, Turner JM (1977). "Bacterial catabolism of threonine. Threonine degradation initiated by l-threonine hydrolyase (deaminating) in a species of Corynebacterium." Biochem J 164(3);579-587. PMID: 16743051

Calhoun73: Calhoun DH, Rimerman RA, Hatfield GW (1973). "Threonine deaminase from Escherichia coli. I. Purification and properties." J Biol Chem 1973;248(10);3511-6. PMID: 4573981

Gollop89: Gollop N, Damri B, Barak Z, Chipman DM (1989). "Kinetics and mechanism of acetohydroxy acid synthase isozyme III from Escherichia coli." Biochemistry 28(15);6310-7. PMID: 2675968

Grimminger79: Grimminger H, Umbarger HE (1979). "Acetohydroxy acid synthase I of Escherichia coli: purification and properties." J Bacteriol 1979;137(2);846-53. PMID: 370104

Komatsubara78: Komatsubara S, Murata K, Kisumi M, Chibata I (1978). "Threonine degradation by Serratia marcescens." J Bacteriol 135(2);318-23. PMID: 355220

LeePeng79: Lee-Peng FC, Hermodson MA, Kohlhaw GB (1979). "Transaminase B from Escherichia coli: quaternary structure, amino-terminal sequence, substrate specificity, and absence of a separate valine-alpha-ketoglutarate activity." J Bacteriol 1979;139(2);339-45. PMID: 378964

Myers61: Myers JW (1961). "Dihydroxy acid dehydrase: an enzyme involved in the biosynthesis of isoleucine and valine." J Biol Chem 236;1414-8. PMID: 13727223

Neidhardt96: Neidhardt FC, Curtiss III R, Ingraham JL, Lin ECC, Low Jr KB, Magasanik B, Reznikoff WS, Riley M, Schaechter M, Umbarger HE "Escherichia coli and Salmonella, Cellular and Molecular Biology, Second Edition." American Society for Microbiology, Washington, D.C., 1996.

Ratzkin72: Ratzkin B, Arfin S, Umbarger HE (1972). "Isoleucine and valine metabolism in Escherichia coli. 18. Induction of acetohydroxy acid isomeroreductase." J Bacteriol 112(1);131-41. PMID: 4562389

Umbarger57: Umbarger HE, Brown B (1957). "Threonine deamination in Escherichia coli. II. Evidence for two L-threonine deaminases." J Bacteriol 73(1);105-12. PMID: 13405870

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Adelberg53: Adelberg EA, Umbarger HE (1953). "Isoleucine and valine metabolism in Escherichia coli. V. alpha-Ketoisovaleric acid accumulation." J Biol Chem 205(1);475-82. PMID: 13117924

AlexanderCaudle90: Alexander-Caudle C, Latinwo LM, Jackson JH (1990). "Acetohydroxy acid synthase activity from a mutation at ilvF in Escherichia coli K-12." J Bacteriol 1990;172(6);3060-5. PMID: 2188950

Andersen01: Andersen DC, Swartz J, Ryll T, Lin N, Snedecor B (2001). "Metabolic oscillations in an E. coli fermentation." Biotechnol Bioeng 75(2);212-8. PMID: 11536144

Bairoch93: Bairoch A, Boeckmann B (1993). "The SWISS-PROT protein sequence data bank, recent developments." Nucleic Acids Res. 21:3093-3096. PMID: 8332529

Barak12: Barak Z, Chipman DM (2012). "Allosteric regulation in Acetohydroxyacid Synthases (AHASs)--different structures and kinetic behavior in isozymes in the same organisms." Arch Biochem Biophys 519(2);167-74. PMID: 22198286

Barak87: Barak Z, Chipman DM, Gollop N (1987). "Physiological implications of the specificity of acetohydroxy acid synthase isozymes of enteric bacteria." J Bacteriol 169(8);3750-6. PMID: 3301814

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

Brown78: Brown OR, Yein F (1978). "Dihydroxyacid dehydratase: the site of hyperbaric oxygen poisoning in branch-chain amino acid biosynthesis." Biochem Biophys Res Commun 85(3);1219-24. PMID: 367373

Burns95: Burns DM, Burger MJ, Beacham IR (1995). "Silent genes in bacteria: the previously designated 'cryptic' ilvHI locus of 'Salmonella typhimurium LT2' is active in natural isolates." FEMS Microbiol Lett 131(2);167-72. PMID: 7557326

Chen13: Chen L, Chen Z, Zheng P, Sun J, Zeng AP (2013). "Study and reengineering of the binding sites and allosteric regulation of biosynthetic threonine deaminase by isoleucine and valine in Escherichia coli." Appl Microbiol Biotechnol 97(7);2939-49. PMID: 22669632

Chunduru89: Chunduru SK, Mrachko GT, Calvo KC (1989). "Mechanism of ketol acid reductoisomerase--steady-state analysis and metal ion requirement." Biochemistry 28(2);486-93. PMID: 2653423

Dailey86: Dailey FE, Cronan JE (1986). "Acetohydroxy acid synthase I, a required enzyme for isoleucine and valine biosynthesis in Escherichia coli K-12 during growth on acetate as the sole carbon source." J Bacteriol 1986;165(2);453-60. PMID: 3511034

Daniels92: Daniels DL, Plunkett G, Burland V, Blattner FR (1992). "Analysis of the Escherichia coli genome: DNA sequence of the region from 84.5 to 86.5 minutes." Science 1992;257(5071);771-8. PMID: 1379743

Datta87: Datta P, Goss TJ, Omnaas JR, Patil RV (1987). "Covalent structure of biodegradative threonine dehydratase of Escherichia coli: homology with other dehydratases." Proc Natl Acad Sci U S A 1987;84(2);393-7. PMID: 3540965

De74: De Felice M, Guardiola J, Esposito B, Iaccarino M (1974). "Structural genes for a newly recognized acetolactate synthase in Escherichia coli K-12." J Bacteriol 120(3);1068-77. PMID: 4612003

De78: De Felice M, Squires C, Levinthal M (1978). "A comparative study of the acetohydroxy acid synthase isoenzymes of Escherichia coli K-12." Biochim. Biophys. Acta 541;9-17.

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

Duan09: Duan X, Yang J, Ren B, Tan G, Ding H (2009). "Reactivity of nitric oxide with the [4Fe-4S] cluster of dihydroxyacid dehydratase from Escherichia coli." Biochem J 417(3);783-9. PMID: 18945212

Eisenstein91: Eisenstein E (1991). "Cloning, expression, purification, and characterization of biosynthetic threonine deaminase from Escherichia coli." J Biol Chem 1991;266(9);5801-7. PMID: 2005118

Eisenstein94: Eisenstein E, Yu HD, Schwarz FP (1994). "Cooperative binding of the feedback modifiers isoleucine and valine to biosynthetic threonine deaminase from Escherichia coli." J Biol Chem 269(47);29423-9. PMID: 7961922

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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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