Abstract
This review provides a description of the biochemistry and enzymology of the α-aminoadipate pathway for lysine biosynthesis in fungi. The α-aminoadipate pathway is unique to fungi and is thus a potential target for the rational design of antifungal drugs. The present state of knowledge of the mechanisms of the seven enzymes in the pathway is presented, as well as detailed information with respect to structures and mechanisms of homocitrate synthase, saccharopine reductase, and saccharopine dehydrogenase.
References
Zabriskie, T. M. and Jackson, M. D. (2000) Lysine biosynthesis and metabolism in fungi. Nat. Prod. Rep. 17, 85–97.
Umbargar, H. E. (1978) Amino acid biosynthesis and its regulation. Annu. Rev. Biochem. 47, 533–606.
Bhattacharjee, J. K. (1985) α-Aminoadipate pathway for the biosynthesis of lysine in lower eukaryotes. Crit. Rev. Microbiol. 12, 131–151.
Bhattacharjee, J. K. (1992) Evolution of α-aminoadipate pathway for the synthesis of lysine in fungi, in Handbook of Evolution of Metabolic Function (Mortlock, R. P., ed.), CRC Press, Boca Raton, FL, pp. 47–80.
Vogel, H. J. (1960) Two modes lysine synthesis among lower fungi: evolutionary significance. Biochim. Biophys. Acta 41, 172–174.
Berges, D. A., DeWolf, W. E., Jr., Dunn, G. L., et al. (1986) Peptides of 2-aminopimelic acid: antibacterial agents that inhibit diaminopimelic acid biosynthesis. J. Med. Chem. 29, 89–95.
Bhattacharjee, J. K. and Strassman, M. (1967) Accumulation of tricarboxylic acids related to lysine biosynthesis in a yeast mutant. J. Biol. Chem. 242, 2542–2546.
Gaillardin, C. M., Ribert, A. M. and Heslot, H. (1982) Wild type and mutant forms of homoisocitric dehydrogenase in the yeast Saccharomycopsis lipolytica. Eur. J. Biochem. 128, 489–494.
Ye, Z. H. and Bhattacharjee, J. K. (1988) Lysine biosynthesis pathway and biochemical blocks of lysine auxotrophs of Schizosaccharomyces pombe. J. Bacteriol. 170, 5968–5970.
Glass, J. and Bhattacharjee, J. K. (1971) Biosynthesis of lysine in R. glutinis: accumulation of homocitric, homoaconitic, and homoisocitric acids in a leaky mutant. Genetics 67, 365–376.
Kunze, G., Bode, R., Schmidt, H., Samsonova, I. A., and Birnbaum D. (1987) Identification of a lys2 mutant of C. maltosa by means of transformation. Curr. Genet. 11, 385–391.
Broquist, H. P. (1971) Lysine biosynthesis (yeast). Methods Enzymol. 17, 112–129.
Jaklitsch, W. M. and Kubicek, C. P. (1990) Homocitrate synthase from Penicillium chrysogenum. Localization, purification of the cytosolic isoenzyme, and sensitivity to lysine. Biochem. J. 269, 247–253.
Garrad, R. C. and Bhattacharjee, J. K. (1992) Lysine biosynthesis in selected pathogenic fungi: characterization of lysine auxotrophs and the cloned LYS1 gene of Candida albicans. J. Bacteriol. 174, 7379–7384.
Andi, B., West, A. H., and Cook, P. F. (2004) Stabilization and characterization of histidine-tagged homocitrate synthase from Saccharomyces cerevisiae. Arch. Biochem. Biophys. 421, 243–254.
Strassman, M. and Weinhouse, S. (1953) Biosynthetic pathways. III. The biosynthesis of lysine Torulopsis utilis. J. Am. Chem. Soc. 75, 1680–1684.
Vogel, H. J. (1965) Lysine biosynthesis and evolution, in Handbook of Evolving Genes and Proteins (Bryson, V., ed.), Academic Press, New York, pp. 25–40.
Nishida, H., Nishiyama, M., Kobashi, N., Kosuge, T., Hoshino, T., and Yamane, H. (1999) A prokaryotic gene cluster involved in synthesis of lysine through the aminoadipate pathway: a key to the evolution of amino acid biosynthesis. Genome Res. 9, 1175–1183.
Cunin, R., Glandsorff, N., Pierard, A., and Stalon, V. (1986) Biosynthesis and metabolism of arginine in bacteria. Microbiol. Rev. 50, 314–352.
Jacq, C., Alt-Morbe, J., Andre, B., et al. (1997) The nucleotide sequence of saccharomyces cerevisiae chromosome IV. Nature 387, 75–78.
Philippsen, P., Kleine, K., Pohlmann, R., et al. (1997) The nucleotide sequence of Saccharomyces cerevisiae chromosome XIV and its evolutionary implications. Nature 387, 93–98.
Tettelin, H., Agostoni Carbone, M. L., Albermann, K., et al. (1997) The nucleotide sequence of Saccharomyces cerevisiae chromosome VII. Nature 387, 81–84.
Borell, C. W., Urrestarazu, L. A., and Bhattacharjee, J. K. (1984) Two unlinked lysine genes (LYS9 and LYS14) are required for the synthesis of saccharopine reductase in Saccharomyces cerevisiae. J. Bacteriol. 159, 429–432.
Wang, L., Okamoto, S., and Bhattacharjee, J. K. (1989) Cloning and physical characterization of linked lysine genes (LYS4, LYS15) of S. cerevisiae. Curr. Genet. 16, 7–12.
Urrestarazu, L. A., Borell, C. W., and Bhattacharjee, J. K. (1985) General and specific controls of lysine biosynthesis in Saccharomyces cerevisiae. Curr. Genet. 9, 341–344.
Irvin, S. D. and Bhattacharjee, J. K. (1998) A unique fungal lysine biosynthesis enzyme shares a common ancestor with tricarboxylic acid cycle and leucine biosynthetic enzymes found in diverse organisms. J. Mol. Evol. 46, 401–408.
Karsten, W. E. and Cook, P. F. (2000) Pyridine nucleotide-dependent β-hydroxyacid oxidative decarboxylases: an overview. Protein Pept. Lett. 7, 281–286.
Ye, Z. H., Garrad, R. C., Winston, M. K. and Bhattacharjee, J. K. (1991) Use of alpha-aminoadipate and lysine as sole nitrogen source by Schizosaccharomyces pombe and selected pathogenic fungi. J. Basic Microbiol. 31, 149–156.
Nishida, H. and Nishiyama, M. (2000) What is characteristic of fungal lysine synthesis through the α-aminoadipate pathway?. J. Mol. Evol. 51, 299–302.
Kosuge, T. and Hoshino, T. (1998) Lysine is synthesized through the α-aminoadipate pathway in Thermus thermophilus. FEMS Microbiol. Lett. 169, 361–367.
Kobashi, N., Nishiyama, M., and Tanokura, M. (1999) Aspartate kinase-independent lysine synthesis in an extremely thermophilic bacterium, Thermus thermophilus: lysine is synthesized via α-aminoadipic acid not via diaminopimelic acid. J. Bacteriol. 181, 1713–1718.
Baldwin, J. E., Shiau, C., Byford, M., and Schofield, C. J. (1994) Substrate specificity of l-delta-(alpha-aminoadipoyl)-l-cysteinyl-D-valine synthetase from Cephalosporium acremonium: demonstration of the structure of several unnatural tripeptide products. Biochem. J. 301, 367–372.
Palmer D. R., Balogh, H., Ma, G., Zhou, X., Marko, M., and Kaminskyj, S. G. (2004) Synthesis and antifungal properties of compounds which target the alpha-aminoadipate pathway. Pharmazie 59, 93–98.
Ramos, F., Dubois, E., and Piérard, A. (1988) Control of enzyme synthesis in the lysine biosynthetic pathway of Saccharomyces cerevisiae. Evidence for a regulatory role of gene LYS14. Eur. J. Biochem. 171, 171–176.
Wolfner, M., Yep, D., Messenguy, F., and Fink, G. R. (1975) Integration of amino acid biosynthesis into the cell cycle of Saccharomyces cerevisiae. J. Mol. Biol. 96, 273–290.
Becker, B., Feller, A., El Alami, M., Dubois, E., and Pierard, A. (1998) A nonameric core sequence is required upstream of the LYS genes of Saccharomyces cerevisiae for Lys14p-mediated activation and apparent repression by lysine. Mol. Microbiol. 29, 151–163.
Ramos, F., Verhasselt, P., Feller, A., et al. (1996) Identification of a gene encoding a homocitrate synthase isoenzyme of Saccharomyces cerevisiae. Yeast 12, 1315–1320.
Tucci, A. F. and Ceci, L. N. (1972) Homocitrate synthase from yeast. Arch. Biochem. Biophys. 153, 742–750.
Ramos, F., and Wiame, J. M. (1985) Mutation affecting the specific regulatory control of lysine biosynthetic enzymes in Saccharomyces cerevisiae. Mol. Gen. Genet. 200, 291–294.
Feller, A., Ramos, F., Piérard, A., and Bubois, E. (1999) In Saccharomyces cerevisiae, feedback inhibition of homocitrate synthase isoenzymes by lysine modulates the activation of LYS gene expression by Lys14p. Eur. J. Biochem. 261, 163–170.
Harrison, S. C. (1991) A structural taxonomy of DNA-binding domains. Nature 353, 715–719.
Vallee, B. L., Coleman, J. E., and Auld, D. S. (1991) Zinc fingers, zinc clusters, and zinc twists in DNA-binding protein domains. Proc. Natl. Acad. Sci. USA 88, 999–1003.
Marmorstein, R., Carey, M., Ptashne, M., and Harrison, S. C. (1992) DNA recognition by GAL4: structure of a protein-DNA complex. Nature 356, 408–414.
Marmorstein, R., and Harrison, S. C. (1994) Crystal structure of a PPR1-DNA complex: DNA recognition by proteins containing a Zn2Cys6 binuclear cluster. Genes Dev. 8, 2504–2512.
Schejerling, P. and Holmberg, S. (1996) Comparative amino acid sequence analysis of the C6 zinc cluster family of transcriptional regulators. Nucleic Acids Res. 24, 4599–4607.
Bañuelos, O., Casqueiro, J., Gutiérrez, S., and Mart (2000) Overexpression of the lys1 gene in Penicillium chrysogenum: homocitrate synthase levels, α-aminoadipic acid pool and penicillin production. Appl. Microbiol. Biotechnol. 54, 69–77.
Wulandari, A. P., Miyazaki, J., Kobashi, N., Nishiyama, M., Hoshino, T., and Yamane, H. (2002) Characterization of bacterial homocitrate synthase involved in lysine biosynthesis. FEBS Lett. 522, 35–40.
Andi, B., West, A. H., and Cook, P. F. (2005) Regulatory mechanism of histidine-tagged homocitrate synthase from Saccharomyces cerevisiae: I. Kinetic studies. J. Biol. Chem. 280, 31,624–31,632.
Andi, B. and Cook, P. F. (2005) Regulatory mechanism of histidine-tagged homocitrate synthase form Saccharomyces cerevisiae: II. Theory. J. Biol. Chem. 280, 31,633–31,640.
Friedrich, C. G. and Demain, A. L. (1977) Homocitrate synthase as the crucial site of the lysine effect on penicillin biosynthesis. J. Antibiot. 30, 760–761.
Somerson, N. L., Demain, A. L., and Nunheimer, T. D. (1961) Reversal of lysine inhibition of penicillin production by α-aminoadipic acid. Arch. Biochem. Biophys. 93, 238–241.
Luengo, J. M., Revilla, G., López, M. J., Villanueva, J. R., and Mart homocitrate synthase by lysine in Penicillium chrysogenum. J. Bacteriol. 144, 869–976.
Tracy, J. W. and Kohlhaw, G. B. (1975) Reversible, coenzyme-A-mediated inactivation of biosynthetic condensing enzymes in yeast: a possible regulatory mechanism. Proc. Nat. Acad. Sci. USA 72, 1802–1806.
Hampsey, D. M. and Kohlaw, G. B. (1981) Inactivation of yeast α-isopropyl malate synthase by CoA. J. Biol. Chem. 256, 3791–3796.
Tracy, J. W. and Kohlhaw, G. B. (1977) Evidence for two distinct CoA binding sites on yeast α-isopropylmalate synthase. J. Biol. Chem. 252 4085–4091.
Kohlhaw, G. B. (2003) Leucine biosynthesis in fungi: entering metabolism through the back door. Microbiol. Mol. Biol. Rev. 67, 1–15.
Tan-Wilson, A. and Kohlhaw, G. B. (1978) Specific, reversible inactivation of yeast β-hydroxy-β-methylglutaryl-CoA reductase by CoA. Biochem. Biophys. Res. Commun. 85, 70–76.
Gilbert, H. F. and Stewart, M. D. (1981) Inactivation of hydroxymethylglutaryl-CoA reductase from yeast by coenzyme A disulfide. J. Biol. Chem. 256, 1782–1785.
Li, J. J. (2003) Name Reactions: A Collection of Detailed Reaction Mechanism, 2nd ed., Springer, Berlin.
Alter, G. M., Casazza, J. P., Zhi, W., Memeth, P., Srere, P. A., and Evans, C. T. (1990) Mutation of essential catalytic residues in pig citrate synthase. Biochemistry 29, 7557–7563.
Karpusas, M., Branchaud, B., and Remington, S. J. (1990) Proposed mechanism for the condensation reaction of citrate synthase: 1.9 Å structure of the ternary complex with oxaloacetate and carboxymethyl coenzyme A. Biochemistry 29, 2213–2219.
Mulholland, A. J., Lyne, P. D., and Karplus, M. (2000) Ab initio QM/MM study of the citrate synthase mechanism: a low-barrier hydrogen bond is not involved. J. Am. Chem. Soc. 122, 534–535.
Evans, C. T., Kurz, L. C., Remington, S. J., and Srere, P. A. (1996) Active site mutants of pig citrate synthase: effects of mutations on the enzyme catalytic and structural properties. Biochemistry 35, 10,661–10,672.
Simth, C. V., Huang, C.-C., Miczak, A., Russell, D. G., Sacchettini, J. C., and Höner zu Bentrup, K. (2003) Biochemical and structural studies of malate synthase from Mycobacterium tuberculosis. J. Biol. Chem. 278, 1735–1743.
Anstrom, D. M., Kallio, K., and Remington, S. J. (2003) Structure of the Escherichia coli malate synthase G:pyruvate:acetyl-coenzyme A abortive ternary complex at 1.95 Å resolution. Protein Sci. 12, 1822–1832.
Howard, B. R., Endrizzi, J. A., and Remington, S. J. (2000) Crystal structure of Escherichia coli malate synthase G complexed with magnesium and glyoxylate at 2.0 Å resolution: mechanistic implications. Biochemistry 39, 3156–3168.
Koon, N., Squire, C. J., and Baker, E. N. (2004) Crystal structure of LeuA from Mycobacterium tuberculosis, a key enzyme in leucine biosynthesis. Proc. Nat. Acad. Sci. USA 101, 8295–8300.
Chen, S., Brockenbrough, J. S., Dove, J. E., and Aris, J. P. (1997) Homocitrate synthase is located in the nucleus in the yeast Saccharomyces cerevisiae. J. Biol. Chem. 272, 10,839–10,846.
Bañuelos, O., Casqueiro, J., Steidl, S., Gutirrez, S., Brakhage, A., and Martin, J. F. (2002) Subcellular localization of the homocitrate synthase in Penicillium chrysogenum. Mol. Genet. Genomics 266, 711–719.
Verhasselt, P., Voet, M., and Volckaert, G. (1995) New open reading frames, one of which is similar to the nifV gene of Azotobacter vinelandii, found on a 12.5 kbp fragment of chromosome IV of Saccharomyces cerevisiae. Yeast 11, 961–966.
Shah, V. K. and Brill, W. J. (1977) Isolation of an iron-molybdenum cofactor from nitrogenase. Proc. Natl. Acad. Sci. USA 74, 3249–3253.
Zheng, L. M., White, R. H., and Dean, D. R. (1997) Purification of the Azotobacter vinelandii nifV-encoded homocitrate synthase. J. Bacteriol. 179, 5963–5966.
Gaillardin, C. M., Poirier, L., and Heslot, H. (1976) A kinetic study of homocitrate synthase activity in the yeast Saccharomycopsis lipolytica. Biochim. Biophys. Acta 422, 390–406.
Andi, B., West, A. H., and Cook, P. F. (2004) Kinetic mechanism of histidine-tagged homocitrate synthase from Saccharomyces cerevisiae. Biochemistry 43, 11,790–11,795.
Voet, D. and Voet, J. G. (2004) Biochemistry, 3rd ed., John Wiley, New York.
Perez-campo, F.-M., Nicaud, J.-M., Gaillardin, C., and Dominguez, A. (1996) Cloning and sequencing of the LYS1 gene encoding homocitrate synthase in the yeast Yarrowia lipolytica. Yeast 12, 1459–1469.
Thomas, U., Kalyanpur, M. G., and Stevens, C. M. (1966) The absolute configuration of homocitric acid (2-hydroxy-1,2,4-butanetricarboxylic acid), an intermediate in lysine biosynthesis. Biochemistry 5, 2513–2516.
Copley, R. R. and Bork, P. (2000) Homology among (betaalpha) (8) barrels: implications for the evolution of metabolic pathways. J. Mol. Biol. 303, 627–640.
Vallee, B. L., and Auld, D. S. (1990) Active-site zinc ligands and activated H2O of zinc enzymes. Proc. Natl. Acad. Sci. USA 87, 220–224.
Vallee, B., and Auld, D. S. (1989) Short and long spacer sequences and other structural features of zinc binding sites in zinc enzymes. FEBS Lett. 257, 138–140.
Vallee, B., and Auld, D. S. (1990) Zinc coordination, function, and structure of zinc enzymes and other proteins. Biochemistry 29, 5647–5659.
Beinert, H., Kennedy, M. C., and Stout, C. D. (1996) Aconitase as iron-sulfur protein, enzyme, and iron-regulatory protein. Chem. Rev. 96, 2335–2373.
Grodsky, N. B., Soundar, S., and Colman, R. F. (2000) Evaluation by site-directed mutagenesis of aspartic acid residues in the metal site of pig heart NADP-dependent isociatrate dehydrogenase. Biochemistry 39, 2193–2200.
Matsuda, M. and Ogur, M. (1969) Separation and specificity of the yeast glutamate-α-ketoadipate transaminase. J. Biol. Chem. 244, 3352–3358.
Matsuda, M. and Ogur, M. (1969) Enzymatic and physiological properties of the yeast glutamate-α-ketoadipate transaminase. J. Biol. Chem. 244, 5153–5158.
Sagisaka, S. and Shimura, K. (1962) Studies in lysine biosynthesis. IV. Mechanism of activation and reduction of α-aminoadipic acid. J. Biochem. 52, 155–161.
Larson, R. L., Sandine, W. D., and Broquist, H. P. (1963) Enzymatic reduction of α-aminoadipic acid: relation to lysine biosynthesis. J. Biol. Chem. 238, 275–282.
Sinha, A. K. and Bhattacharjee, J. K. (1971) Lysine biosynthesis in Saccharomyces, conversion of α-aminoadipate into α-aminoadipic δ-semialdehyde. Biochem. J. 125, 743–749.
Suyarna, K., Seah, L., Bhattacharjee, V., and Bhattacharjee, J. K. (1998) Molecular analysis of the LYS2 gene of Candida albicans: homology to peptide antibiotic synthetases and the regulation of the α-amioadipate reductase. Curr. Genet. 33, 268–275.
Lambalot, R. H., Gehring, A. M., Flugel, R. S., et al. (1996) A new enzyme superfamily—the phosphopatetheinyl transferases. Chem. Biol. 3, 932–936.
Ehmann, D. E., Gehring, A. M., and Walsh, C. T. (1999) Lysine biosynthesis in Saccharomyces cerevisiae: mechanism of α-aminoadipate reductase (LYS2) involves posttranslational phosphopantetheinylation by LYS5. Biochemistry 38, 6171–6177.
Praphanphoj, V., Sacksteder, K. A., Gould, S. J., Thomas, G. H., and Geraghty, M. T. (2001) Identification of the α-aminoadipic semialdehyde dehydrogenase-phosphopantetheinyl transferase gene, the human ortholog of the yeast LYS5 gene. Mol. Genet. Metab. 72, 336–342.
Guo, S., Evans, S. A., Wilkes, M. B., and Bhattacharjee, J. K. (2001) Novel posttranslational activation of the LYS2-encoded α-aminoadipate reductase for biosynthesis of lysine and site-directed mutational analysis of conserved amino acid residues in the activation domain of Candida albicans. J. Bacteriol. 183, 7120–7125.
Brunhuber, N. M., and Blanchard, J. S. (1994) The biochemistry and enzymology of amino acid dehydrogenases. Crit. Rev. Biochem. Mol. Biol. 29, 415–467.
Weiss, P. M., Chen, C.-Y., Cleland, W. W., and Cook, P. F. (1998) Use of primary deuterium and 15N isotope effects to deduce the relative rates of steps in the mechanisms of alanine and glutamate dehydrogenases. Biochemistry 27, 4814–4822.
Rife, J. E., and Cleland, W. W. (1980a) Kinetic mechanism of glutamate dehydrogenase. Biochemistry 19, 2321–2328.
Schroder, I., Vadas, A., Johnson, E., Lim, S., and Monbouquette, H. G. (2004) A novel archaeal alanine dehydrogenase homologous to ornithine cyclodeaminase and μ-crystallin. J. Bacteriol. 186, 7680–7689.
Ohshima, T. and Soda, K. (1979) Purification and characterization of alanine dehydrogenase from Bacillus sphaericus. Eur. J. Biochem. 100, 29–39.
Alizade, M. A., Bressler, R., and Brendel, K. (1975) Stereochemistry of the hydrogen transfer to NAD catalyzed by (S)alanine dehydrogenase from Bacillus subtilis. Biochim. Biophys. Acta 397, 5–8.
Hashimoto, H., Misono, H., Nagata, S., and Nagasaki, S. (1989) Activation of l-lysine ε-dehydrogenase from Agrobacterium tumefaciens by several amino acids and monocarboxylates. J. Biochem. 106, 76–80.
Scapin, G., Reddy, S. G., and Blanchard, J. S. (1996) Three-dimensional structure of meso-diaminopimelic acid dehydrogenase from Corynebacterium glutamicum. Biochemistry 35, 13,540–13,551.
Johansson, E., Steffens, J. J., Lindqvist, Y., and Schneider, G. (2000) Crystal structure of saccharopine reductase from Magnaporthe grisea, an enzyme of the α-aminoadipate pathway of lysine biosynthesis. Struct. Fold. Des. 8, 1037–1047.
Fujioka, M. and Takata, Y. (1979) Stereospecificity of hydrogen transfer in the saccharopine dehydrogenase reaction. Biochim. Biophys. Acta 570, 210–212.
Sugimoto, K. and Fujioka, M. (1984) Chemical mechanism of saccharopine dehydrogenase (NAD+, l-lysine-forming) as deduced form initial rate pH studies. Arch. Biochem. Biophys. 230, 553–559.
Stillman, T. J., Baker, P. J., Britton, K. L., and Rice, D. W. (1993) Conformational flexibility in glutamate dehydrogenase. Role of water in substrate recognition and catalysis. J. Mol. Biol. 234, 1131–1139.
Baker, P. J., Turnbull, A. P., Sedelnikova, S. E., Stillman, T. J., and Rice, D. W. (1995) A role for quaternary structure in the substrate specificity of leucine dehydrogenase. Structure 3, 693–705.
Baker, P. J., Sawa, Y., Shibata, H., Sedelnikova, S. E., and Rice, D. W. (1998) Analysis of the structure and substrate binding of Phormidium lapideum alanine dehydrogenase. Nat. Struct. Biol. 5, 561–567.
Vanhooke, J. L., Thoden, J. B., Brunhuber, N. M. W., Blanchard, J. S., and Holden, H. M. (1999) Phenylalanine dehydrogenase from Rhodococcus sp. M4: high-resolution X-ray analyses of inhibitory ternary complexes reveal key features in the oxidative deamination mechanism. Biochemistry 38, 2326–2339.
Baker, P. J., Waugh, M. L., Wang, X.-G., et al. (1997) Determinants of the substrate specificity in the superfamily of amino acid dehydrogenases. Biochemistry 36, 16,109–16,115.
Jones, E. W. and Fink, G. R. (1982) Regulation of amino acid and nucleotide synthesis in yeast, in Molecular Biology of the Yeast Saccharomyces, Metabolism and Gene Regulation (Strathern, J. N., Jones, E. W., and Broach, J. R., eds.), Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, pp. 181–299.
Storts, D. R. and Bhattacharjee, J. K. (1987) Purification and properties of saccharopine dehydrogenase (glutamate forming) in the Saccharomyces cerevisiae lysine biosynthetic pathway. J. Bacteriol. 169, 416–418.
Jones, E. E. and Broquist, H. P. (1966) Saccharopine, an intermediate of the aminoadipic acid pathway of lysine biosynthesis. III. Aminoadipic semialdehyde-glutamate reductase. J. Biol. Chem. 241, 3430–3434.
Johansson, E., Steffens, J. J., Emptage, M., Lindqvist, Y., and Schneider, G. (2000) Cloning, expression, purification and crystallization of saccharopine reductase from Magnaporthe grisea. Acta Crystallogr. D Biol. Crystallogr. 56, 662–664.
Andi, B., Cook, P. F., and West, A. H. (2006) Crystal structure of the histidine-tagged saccharopine dehydrogenase (l-Glu forming) from Saccharomyces cerevisiae at 1.7Å resolution. Cell Biochem. Biophys. 46, 17–26.
Talbot, N. J. (1995) Having a blast: exploring the pathogenicity of Magnaporthe grisea. Trends Microbiol. 3, 9–16.
Rossmann, M. G., Liljas, A., Branden, C. I., and Banaszak, L. J. (1975) Evolutionary and structural relationship among dehydrogenases. Enzymes 11, 51–102.
Ogawa, H. and Fujioka, M. (1978) Purification and characterization of saccharopine dehydrogenase from baker's yeast. J. Biol. Chem. 253, 3666–3670.
Ogawa, H., Okamoto, M., and Fujioka, M. (1979) Chemical modification of the active site sulfhydryl group of saccharopine dehydrogenase (l-lysine-forming). J. Biol. Chem. 254, 7030–7035.
Ford, R. A., and Bhattacharjee, J. K. (1995) Molecular properties of the lys1+gene and the regulation of α-aminoadipate reductase in Schizosaccharomyces pombe. Curr. Genet. 28, 131–137.
Fujioka, M. and Nakatani, Y. (1974) Saccharopine dehydrogenase, a kinetic study of coenzyme binding. J. Biol. Chem. 249, 6886–6891.
Saunders, P. P. and Broquist, H. P. (1966) Saccharopine, an intermediate of the aminoadipic acid pathway of lysine biosynthesis, saccharopine dehydrogenase. J. Biol. Chem. 241, 3435–3440.
Fujioka, M. and Nakatani, Y. (1972) Saccharopine dehydrogenase, interaction with substrate analogues. Eur. J. Biochem. 25, 301–307.
Fujioka, M. and Tanaka, M. (1978) Enzymic and chemical synthesis of ε-N-(l-propionyl-2)-l-lysine. Eur. J. Biochem. 90, 297–300.
Cleland, W. W. (1963) The kinetics of enzyme-catalyzed reactions with two or more substrates. Biochim. Biophys. Acta 67, 173–187.
Fujioka, M. (1975) Saccharopine dehydrogenase, substrate inhibition studies. J. Biol. Chem. 250, 8986–8989.
Fujioka, M. and Nakatani, Y. (1970) A kinetic study of saccharopine dehydrogenase reaction. Eur. J. Biochem. 16, 180–186.
Sugimoto, K. and Fujioka, M. (1978) The reaction of pyruvate with saccharopine dehydrogenase. Eur. J. Biochem. 90, 301–307.
Fujioka, M., Takata, Y., Ogawa, H., and Okamoto, M. (1979) The inactivation of saccharopine dehydrogenase (l-lysine-forming) by diethyl pyrocarbonate. J. Biol. Chem. 255, 937–942.
Ogawa, H. and Fujioka, M. (1980) The reaction of pyridoxal-5′-phosphate with an essential lysine residue of saccharopine dehydrogenase (l-lysine-forming). J. Biol. Chem. 255, 7420–7425.
Fujioka, M. and Takata, Y. (1981) Role of arginine residue in saccharopine dehydrogenase (l-lysine-forming) from baker's yeast. Biochemistry 20, 468–472.
Ogawa, H., Hase, T., and Fujioka, M. (1980) Amino acid sequence of a peptide containing an essential cysteine residue of yeast saccharopine dehydrogenase (l-lysine-forming). Biochim. Biophys. Acta 623, 225–228.
Hammer, T., Bode, R., Schmidt, H., and Birnbaum, D. (1991) Distribution of three lysine-catabolizing enzymes in various yeast species. J. Basic Microbiol. 31, 43–49.
Author information
Authors and Affiliations
Corresponding authors
Rights and permissions
About this article
Cite this article
Xu, H., Andi, B., Qian, J. et al. The α-aminoadipate pathway for lysine biosynthesis in fungi. Cell Biochem Biophys 46, 43–64 (2006). https://doi.org/10.1385/CBB:46:1:43
Issue Date:
DOI: https://doi.org/10.1385/CBB:46:1:43