If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Locations of Mapped Genes:
|Superclasses:||Biosynthesis → Amino Acids Biosynthesis → Individual Amino Acids Biosynthesis → 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, Chen91c].
Superpathways: superpathway of leucine, valine, and isoleucine biosynthesis
Chen91c: 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
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
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
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
Graczer09: Graczer E, Varga A, Melnik B, Semisotnov G, Zavodszky P, Vas M (2009). "Symmetrical refolding of protein domains and subunits: example of the dimeric two-domain 3-isopropylmalate dehydrogenases." Biochemistry 48(5);1123-34. PMID: 19154118
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