Escherichia coli K-12 substr. MG1655 Pathway: L-leucine biosynthesis
Inferred from experiment

Pathway diagram: L-leucine biosynthesis

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-leucine biosynthesis

Superclasses: BiosynthesisAmino Acids BiosynthesisProteinogenic Amino Acids BiosynthesisL-leucine Biosynthesis

Leucine biosynthesis involves a five-step conversion process starting with the valine precursor 2-keto-isovalerate. The final step in this pathway is catalyzed by two transaminases of broad specificity, IlvE and TyrB.

Both the first enzyme in the pathway, 2-isopropylmalate synthase, and the terminal transaminase TyrB are suppressed by leucine. TyrB is subject to inhibition by the pathway's starting compound, 2-keto-isovalerate, and by one of its off-pathway products, tyrosine. One consequence of this inhibition by 2-keto-isovalerate is that in the absence of IlvE activity, mutations in earlier steps in the pathway cannot be compensated for by any alternate method of introducing 2-ketoisocaproate for conversion to leucine.

Almost all of the genes coding for enzymes in this pathway are controlled by attenuation. Attenuation in operon leuLABCD is effected by a leader region containing four leucines and a transcriptional terminator [Wessler81, Gemmill83]. ilvE is a component of operon ilvLXG_1G_2MEDA, that has an attenuation region containing codons for isoleucine, leucine, and valine, as well as a termination site [Lawther80, Chen91a].

Superpathways: superpathway of branched chain amino acid biosynthesis

Created 02-Feb-1994 by Riley M, Marine Biological Laboratory
Revised 20-Dec-2007 by Caspi R, SRI International
Last-Curated 13-Feb-2007 by Shearer A, SRI International


Chen91a: Chen JW, Harms E, Umbarger HE (1991). "Mutations replacing the leucine codons or altering the length of the amino acid-coding portion of the ilvGMEDA leader region of Escherichia coli." J Bacteriol 173(7);2341-53. PMID: 2007556

Gemmill83: Gemmill RM, Jones JW, Haughn GW, Calvo JM (1983). "Transcription initiation sites of the leucine operons of Salmonella typhimurium and Escherichia coli." J Mol Biol 170(1);39-59. PMID: 6195343

Lawther80: Lawther RP, Hatfield GW (1980). "Multivalent translational control of transcription termination at attenuator of ilvGEDA operon of Escherichia coli K-12." Proc Natl Acad Sci U S A 77(4);1862-6. PMID: 6154938

Vartak91: Vartak NB, Liu L, Wang BM, Berg CM (1991). "A functional leuABCD operon is required for leucine synthesis by the tyrosine-repressible transaminase in Escherichia coli K-12." J Bacteriol 173(12);3864-71. PMID: 1646790

Wessler81: Wessler SR, Calvo JM (1981). "Control of leu operon expression in Escherichia coli by a transcription attenuation mechanism." J Mol Biol 149(4);579-97. PMID: 6171647

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

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

Calvo62: Calvo JM, Kalyanpur MG, Stevens CM (1962). "2-Isopropylmalate and 3-isopropylmalate as intermediates in leucine biosynthesis." Biochemistry 1;1157-61. PMID: 14017963

Carlsen13: Carlsen S, Ajikumar PK, Formenti LR, Zhou K, Phon TH, Nielsen ML, Lantz AE, Kielland-Brandt MC, Stephanopoulos G (2013). "Heterologous expression and characterization of bacterial 2-C-methyl-D-erythritol-4-phosphate pathway in Saccharomyces cerevisiae." Appl Microbiol Biotechnol 97(13);5753-69. PMID: 23636690

Cho04: Cho BK, Park HY, Seo JH, Kinnera K, Lee BS, Kim BG (2004). "Enzymatic resolution for the preparation of enantiomerically enriched D-beta-heterocyclic alanine derivatives using Escherichia coli aromatic L-amino acid transaminase." Biotechnol Bioeng 88(4);512-9. PMID: 15459908

Collier72: Collier RH, Kohlhaw G (1972). "Nonidentity of the aspartate and the aromatic aminotransferase components of transaminase A in Escherichia coli." J Bacteriol 1972;112(1);365-71. PMID: 4404056

deCarvalho05: de Carvalho LP, Argyrou A, Blanchard JS (2005). "Slow-onset feedback inhibition: inhibition of Mycobacterium tuberculosis alpha-isopropylmalate synthase by L-leucine." J Am Chem Soc 127(28);10004-5. PMID: 16011356

deCarvalho06: de Carvalho LP, Blanchard JS (2006). "Kinetic analysis of the effects of monovalent cations and divalent metals on the activity of Mycobacterium tuberculosis alpha-isopropylmalate synthase." Arch Biochem Biophys 451(2);141-8. PMID: 16684501

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

Easton06: Easton JA, Thompson P, Crowder MW (2006). "Time-dependent translational response of E. coli to excess Zn(II)." J Biomol Tech 17(5);303-7. PMID: 17122063

Fotheringham86: Fotheringham IG, Dacey SA, Taylor PP, Smith TJ, Hunter MG, Finlay ME, Primrose SB, Parker DM, Edwards RM (1986). "The cloning and sequence analysis of the aspC and tyrB genes from Escherichia coli K12. Comparison of the primary structures of the aspartate aminotransferase and aromatic aminotransferase of E. coli with those of the pig aspartate aminotransferase isoenzymes." Biochem J 1986;234(3);593-604. PMID: 3521591

Fultz79: Fultz PN, Kwoh DY, Kemper J (1979). "Salmonella typhimurium newD and Escherichia coli leuC genes code for a functional isopropylmalate isomerase in Salmonella typhimurium-Escherichia coli hybrids." J Bacteriol 137(3);1253-62. PMID: 374346

Fultz81: Fultz PN, Kemper J (1981). "Wild-type isopropylmalate isomerase in Salmonella typhimurium is composed of two different subunits." J Bacteriol 1981;148(1);210-9. PMID: 7026530

Gaudet10: Gaudet P, Livstone M, Thomas P (2010). "Annotation inferences using phylogenetic trees." PMID: 19578431

Gelfand77: Gelfand DH, Steinberg RA (1977). "Escherichia coli mutants deficient in the aspartate and aromatic amino acid aminotransferases." J Bacteriol 1977;130(1);429-40. PMID: 15983

Gelfand77a: Gelfand DH, Rudo N (1977). "Mapping of the aspartate and aromatic amino acid aminotransferase genes tyrB and aspC." J Bacteriol 130(1);441-4. PMID: 323238

GOA01: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

GOA06: GOA, SIB (2006). "Electronic Gene Ontology annotations created by transferring manual GO annotations between orthologous microbial proteins."

Goto03: Goto M, Miyahara I, Hayashi H, Kagamiyama H, Hirotsu K (2003). "Crystal structures of branched-chain amino acid aminotransferase complexed with glutamate and glutarate: true reaction intermediate and double substrate recognition of the enzyme." Biochemistry 42(13);3725-33. PMID: 12667063

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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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