This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
|Superclasses:||Biosynthesis → Amino Acids Biosynthesis → Proteinogenic Amino Acids Biosynthesis → L-lysine Biosynthesis|
Six pathways are now recognized in bacteria, most algae, fungi and higher plants for the biosynthesis of lysine. They are divided into two groups - the diaminopimelate (DAP) pathways, and the L-2-aminoadipate pathways.
In the pathways that belong to the DAP group, lysine is produced from aspartate (along with methionine, threonine and isoleucine). All of the DAP group pathways share the upper segments, which include the four steps required for conversion of L-aspartate to (S)-2,3,4,5-tetrahydrodipicolinate. They also share the last step, which is the conversion of the intermediate meso-diaminopimelate (D,L-DAP, or meso-DAP) to lysine. However, these pathways differ in the routes leading from (S)-2,3,4,5-tetrahydrodipicolinate to meso-diaminopimelate. The four variations include:
(I) the succinylase variant (see L-lysine biosynthesis I), which involves succinylated intermediates. In this route (S)-2,3,4,5-tetrahydrodipicolinate is coverted to meso-diaminopimelate in four enzymatic steps.
(II) the acetylase variant (see L-lysine biosynthesis II), which involves acetylated intermediates. This route also involves four enzymatic steps for the conversion of (S)-2,3,4,5-tetrahydrodipicolinate to meso-diaminopimelate.
In addition to lysine, all of the pathways in this group also produce meso-diaminopimelate, which is an important metabolite on its own (for example, as a constituent of bacterial cell wall peptidoglycan).
The two other pathways belong to the L-2-aminoadipate group. They are found in organisms that have no requirement for meso-diaminopimelate, as it is not a component of their cell walls. These pathways also share the first segments, leading to the synthesis of the intermediate L-2-aminoadipate (α-aminoadipate). However, in yeast and fungi, as well as Euglena, the pathway continues with the key enzyme L-2-aminoadipate reductase, leading to the intermediate L-saccharopine (see L-lysine biosynthesis IV), while in prokaryotes the pathway continues in a path similar to bacterial arginine biosynthesis (see L-lysine biosynthesis V).
Most of the bacteria that have been investigated in detail appear to utilize only one of these pathways [Schrumpf91]. A few exceptions include Paenibacillus macerans, in which variants (II) and (III) seem to coexist [Bartlett85], and Corynebacterium glutamicum, in which variant (I) and (III) coexist [Schrumpf91].
Lysine is one of the 10 essential amino acids that mammals are unable to synthesize, and must therefore acquire in their diets.
About This Pathway
The yeast Saccharomyces cerevisiae synthesizes the essential amino acid L-lysine via an L-α-aminoadipate pathway [Zabriskie00]. While some bacteria and archaea synthesize lysine via a similar α-aminoadipate pathway (see L-lysine biosynthesis V), this particular variation is unique to yeast and fungi [Nishida00].
Intermediates in this pathway are often incoporated into secondary metabolites. For example, it has been well-documented that α-aminoadipate is required for penicillin production [Zabriskie00].
Regulation of the lysine biosynthetic pathway in Saccharomyces cerevisiae is an interaction between general amino acid control (via Gcn4p) [Hinnebusch92], feedback inhibition of homocitrate synthase activity by lysine [Feller99], and induction of Lys14p by α-aminoadipate semialdehyde [ElAlami00].
Bartlett85: Bartlett, A. T. M., Whilte, P. J. (1985). "Species of Bacillus that make a vegetative peptidoglycan containing lysine lack diaminopimelate epimerase but have diaminopimelate dehydrogenase." J. Gen. Microbiol. 131:2145-2152.
ElAlami00: El-Alami M, Feller A, Pierard A, Dubois E (2000). "Characterisation of a tripartite nuclear localisation sequence in the regulatory protein Lys14 of Saccharomyces cerevisiae." Curr Genet 38(2);78-86. PMID: 10975256
Feller99: Feller A, Ramos F, Pierard A, Dubois E (1999). "In Saccharomyces cerevisae, feedback inhibition of homocitrate synthase isoenzymes by lysine modulates the activation of LYS gene expression by Lys14p." Eur J Biochem 261(1);163-70. PMID: 10103047
Hinnebusch92: Hinnebusch, A (1992). "General and pathway-specific regulatory mechanisms controlling the synthesis of amino acid biosynthetic enzymes in Saccharomyces cerevisiae." The Molecular and Cellular Biology of the yeast Saccharomyces: Gene Expression, Vol 2, pp. 319-414.
Schrumpf91: Schrumpf B, Schwarzer A, Kalinowski J, Puhler A, Eggeling L, Sahm H (1991). "A functionally split pathway for lysine synthesis in Corynebacterium glutamicium." J Bacteriol 173(14);4510-6. PMID: 1906065
Ehmann99: Ehmann DE, Gehring AM, Walsh CT (1999). "Lysine biosynthesis in Saccharomyces cerevisiae: mechanism of alpha-aminoadipate reductase (Lys2) involves posttranslational phosphopantetheinylation by Lys5." Biochemistry 38(19);6171-7. PMID: 10320345
Goh02: Goh DL, Patel A, Thomas GH, Salomons GS, Schor DS, Jakobs C, Geraghty MT (2002). "Characterization of the human gene encoding alpha-aminoadipate aminotransferase (AADAT)." Mol Genet Metab 76(3);172-80. PMID: 12126930
Hoover88: Hoover TR, Imperial J, Liang JH, Ludden PW, Shah VK (1988). "Dinitrogenase with altered substrate specificity results from the use of homocitrate analogues for in vitro synthesis of the iron-molybdenum cofactor." Biochemistry 1988;27(10);3647-52. PMID: 3044446
Howell00: Howell DM, Graupner M, Xu H, White RH (2000). "Identification of enzymes homologous to isocitrate dehydrogenase that are involved in coenzyme B and leucine biosynthesis in methanoarchaea." J Bacteriol 2000;182(17);5013-6. PMID: 10940051
Howell98: Howell DM, Harich K, Xu H, White RH (1998). "Alpha-keto acid chain elongation reactions involved in the biosynthesis of coenzyme B (7-mercaptoheptanoyl threonine phosphate) in methanogenic Archaea." Biochemistry 1998;37(28);10108-17. PMID: 9665716
Jia06: Jia Y, Tomita T, Yamauchi K, Nishiyama M, Palmer DR (2006). "Kinetics and product analysis of the reaction catalysed by recombinant homoaconitase from Thermus thermophilus." Biochem J 396(3);479-85. PMID: 16524361
Jones66: Jones EE, Broquist HP (1966). "Saccharopine, an intermediate of the aminoadipic acid pathway of lysine biosynthesis. 3. Aminoadipic semialdehyde-glutamate reductase." J Biol Chem 241(14);3430-4. PMID: 4380448
Kobashi99: Kobashi N, Nishiyama M, Tanokura M (1999). "Aspartate kinase-independent lysine synthesis in an extremely thermophilic bacterium, Thermus thermophilus: lysine is synthesized via alpha-aminoadipic acid not via diaminopimelic acid." J Bacteriol 181(6);1713-8. PMID: 10074061
Lombo04: Lombo T, Takaya N, Miyazaki J, Gotoh K, Nishiyama M, Kosuge T, Nakamura A, Hoshino T (2004). "Functional analysis of the small subunit of the putative homoaconitase from Pyrococcus horikoshii in the Thermus lysine biosynthetic pathway." FEMS Microbiol Lett 233(2);315-24. PMID: 15063502
Miyazaki03: Miyazaki J, Kobashi N, Nishiyama M, Yamane H (2003). "Characterization of homoisocitrate dehydrogenase involved in lysine biosynthesis of an extremely thermophilic bacterium, Thermus thermophilus HB27, and evolutionary implication of beta-decarboxylating dehydrogenase." J Biol Chem 278(3);1864-71. PMID: 12427751
Miyazaki04: Miyazaki T, Miyazaki J, Yamane H, Nishiyama M (2004). "alpha-Aminoadipate aminotransferase from an extremely thermophilic bacterium, Thermus thermophilus." Microbiology 150(Pt 7);2327-34. PMID: 15256574
Rubio06: Rubio S, Larson TR, Gonzalez-Guzman M, Alejandro S, Graham IA, Serrano R, Rodriguez PL (2006). "An Arabidopsis mutant impaired in coenzyme A biosynthesis is sugar dependent for seedling establishment." Plant Physiol 140(3);830-43. PMID: 16415216
Showing only 20 references. To show more, press the button "Show all references".
©2015 SRI International, 333 Ravenswood Avenue, Menlo Park, CA 94025-3493