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Pathway Description
Lysine Biosynthesis
Pseudomonas aeruginosa
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2019-08-12
Last Updated: 2019-08-16
Lysine is biosynthesized from L-aspartic acid. L-Aspartic acid can be incorporated into the cell through various methods: C4 dicarboxylate/orotate:H+ symporter, glutamate/aspartate:H+ symporter GltP, dicarboxylate transporter, C4 dicarboxylate/C4 monocarboxylate transporter DauA, and glutamate/aspartate ABC transporter. L-Aspartic acid is phosphorylated by an ATP-driven aspartate kinase resulting in ADP and L-aspartyl-4-phosphate. L-Aspartyl-4-phosphate is then dehydrogenated through an NADPH-driven aspartate semialdehyde dehydrogenase resulting in a release of phosphate, NADP, and L-aspartic 4-semialdehyde (involved in methionine biosynthesis). L-Aspartic 4-semialdehyde interacts with a pyruvic acid through a 4-hydroxy-tetrahydrodipicolinate synthase resulting in a release of hydrogen ion, water, and (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate. The latter compound is then reduced by an NADPH-driven 4-hydroxy-tetrahydrodipicolinate reductase resulting in a release of water, NADP, and (S)-2,3,4,5-tetrahydrodipicolinate, This compound interacts with succinyl-CoA and water through a tetrahydrodipicolinate succinylase resulting in a release of coenzyme A and N-succinyl-2-amino-6-ketopimelate. This compound interacts with L-glutamic acid through an N-succinyldiaminopimelate aminotransferase resulting in oxoglutaric acid and N-succinyl-L,L-2,6-diaminopimelate. The latter compound is then desuccinylated by reacting with water through an N-succinyl-L-diaminopimelate desuccinylase resulting in a succinic acid and L,L-diaminopimelate. This compound is then isomerized through a diaminopimelate epimerase resulting in a meso-diaminopimelate (involved in peptidoglycan biosynthesis I). This compound is then decarboxylated by a diaminopimelate decarboxylase resulting in a release of carbon dioxide and L-lysine. L-Lysine is then incorporated into the lysine degradation pathway. Lysine also regulates its own biosynthesis by repressing dihydrodipicolinate synthase and also by repressing lysine-sensitive aspartokinase 3. Diaminopielate is a precursor for lysine as well as other cell wall components. Synthesis of lysine starts by converting L-aspartic acid (L-aspartate) to L-Aspartyl-4-phosphate by aspartate kinase. L-Aspartyl-4-phosphate transforms to form L-aspartic 4-semialdehyde (L-aspartate semialdehyde) by aspartate semialdehyde dehydrogenase with NADPH. L-aspartic 4-semialdehyde can start the metabolic pathway of synthesis of methionine as well as synthesis of threonine. Aspartate kinase can be regulated by its end product: L-Lysine.
References
Lysine Biosynthesis References
Martin C, Cami B, Yeh P, Stragier P, Parsot C, Patte JC: Pseudomonas aeruginosa diaminopimelate decarboxylase: evolutionary relationship with other amino acid decarboxylases. Mol Biol Evol. 1988 Sep;5(5):549-59. doi: 10.1093/oxfordjournals.molbev.a040515.
Pubmed: 3143046
Stover CK, Pham XQ, Erwin AL, Mizoguchi SD, Warrener P, Hickey MJ, Brinkman FS, Hufnagle WO, Kowalik DJ, Lagrou M, Garber RL, Goltry L, Tolentino E, Westbrock-Wadman S, Yuan Y, Brody LL, Coulter SN, Folger KR, Kas A, Larbig K, Lim R, Smith K, Spencer D, Wong GK, Wu Z, Paulsen IT, Reizer J, Saier MH, Hancock RE, Lory S, Olson MV: Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic pathogen. Nature. 2000 Aug 31;406(6799):959-64. doi: 10.1038/35023079.
Pubmed: 10984043
Hoang TT, Williams S, Schweizer HP, Lam JS: Molecular genetic analysis of the region containing the essential Pseudomonas aeruginosa asd gene encoding aspartate-beta-semialdehyde dehydrogenase. Microbiology. 1997 Mar;143 ( Pt 3):899-907. doi: 10.1099/00221287-143-3-899.
Pubmed: 9084174
Moore RA, Bocik WE, Viola RE: Expression and purification of aspartate beta-semialdehyde dehydrogenase from infectious microorganisms. Protein Expr Purif. 2002 Jun;25(1):189-94. doi: 10.1006/prep.2002.1626.
Pubmed: 12071715
Kaur N, Gautam A, Kumar S, Singh A, Singh N, Sharma S, Sharma R, Tewari R, Singh TP: Biochemical studies and crystal structure determination of dihydrodipicolinate synthase from Pseudomonas aeruginosa. Int J Biol Macromol. 2011 Jun 1;48(5):779-87. doi: 10.1016/j.ijbiomac.2011.03.002. Epub 2011 Mar 10.
Pubmed: 21396954
Itoh Y: Cloning and characterization of the aru genes encoding enzymes of the catabolic arginine succinyltransferase pathway in Pseudomonas aeruginosa. J Bacteriol. 1997 Dec;179(23):7280-90. doi: 10.1128/jb.179.23.7280-7290.1997.
Pubmed: 9393691
Park SM, Lu CD, Abdelal AT: Cloning and characterization of argR, a gene that participates in regulation of arginine biosynthesis and catabolism in Pseudomonas aeruginosa PAO1. J Bacteriol. 1997 Sep;179(17):5300-8. doi: 10.1128/jb.179.17.5300-5308.1997.
Pubmed: 9286980
Lee DG, Urbach JM, Wu G, Liberati NT, Feinbaum RL, Miyata S, Diggins LT, He J, Saucier M, Deziel E, Friedman L, Li L, Grills G, Montgomery K, Kucherlapati R, Rahme LG, Ausubel FM: Genomic analysis reveals that Pseudomonas aeruginosa virulence is combinatorial. Genome Biol. 2006;7(10):R90. doi: 10.1186/gb-2006-7-10-r90. Epub 2006 Oct 12.
Pubmed: 17038190
Nishijyo T, Park SM, Lu CD, Itoh Y, Abdelal AT: Molecular characterization and regulation of an operon encoding a system for transport of arginine and ornithine and the ArgR regulatory protein in Pseudomonas aeruginosa. J Bacteriol. 1998 Nov;180(21):5559-66.
Pubmed: 9791103
Hayden HS, Gillett W, Saenphimmachak C, Lim R, Zhou Y, Jacobs MA, Chang J, Rohmer L, D'Argenio DA, Palmieri A, Levy R, Haugen E, Wong GK, Brittnacher MJ, Burns JL, Miller SI, Olson MV, Kaul R: Large-insert genome analysis technology detects structural variation in Pseudomonas aeruginosa clinical strains from cystic fibrosis patients. Genomics. 2008 Jun;91(6):530-7. doi: 10.1016/j.ygeno.2008.02.005. Epub 2008 Apr 29.
Pubmed: 18445516
Valentini M, Storelli N, Lapouge K: Identification of C(4)-dicarboxylate transport systems in Pseudomonas aeruginosa PAO1. J Bacteriol. 2011 Sep;193(17):4307-16. doi: 10.1128/JB.05074-11. Epub 2011 Jul 1.
Pubmed: 21725012
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 SMP0000794
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