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 → Amines and Polyamines Biosynthesis → Spermidine Biosynthesis|
Some taxa known to possess this pathway include : Campylobacter jejuni , Campylobacter jejuni jejuni 81116 , Vibrio alginolyticus , Vibrio alginolyticus NBRC 15630 = ATCC 17749 , Vibrio cholerae , Vibrio parahaemolyticus , Vibrio vulnificus , Vibrio vulnificus CMCP6
Expected Taxonomic Range: Bacteria
Polyamines are found in bacteria, archaea and eukaryotes and are necessary for normal cellular physiology. They include the diamine putrescine, the triamines spermidine, norspermidine (sym-norspermidine) and sym-homospermidine (homospermidine), and the tetraamine spermine (in [Shaw10] and in [Lee09a]).
Several independent pathways have been identified for the biosynthesis of spermidine. In pathway spermidine biosynthesis I, S-adenosyl 3-(methylthio)propylamine (decarboxylated S-adenosyl-L-methionine) donates an aminopropyl group to putrescine to form spermidine in a reaction catalyzed by spermidine synthase. This pathway is found in most eukaryotes and archaea and in many bacteria.
In this pathway variant, spermidine biosynthesis II, L-aspartate-semialdehyde donates a carboxyaminopropyl group to putrescine to form carboxyspermidine. This reaction is catalyzed by either carboxynorspermidine/carboxyspermidine dehydrogenase (CANSDH) or carboxyspermidine dehydrogenase (CASDH) depending upon species. Likewise, the subsequent decarboxylation of carboxyspermidine to produce spermidine is catalyzed by either carboxynorspermidine/carboxyspermidine decarboxylase (CANSDC) or carboxyspermidine decarboxylase (CASDC) [Lee09a, Hanfrey11] and in [Shaw10].
A spermidine biosynthetic pathway found in hyperthermophiles involves N1-(3-aminopropyl)agmatine as an intermediate [Morimoto10, Ohnuma05] (see pathway spermidine biosynthesis III). In addition, some bacteria biosynthesize the triamine sym-homospermidine rather than spermidine [Shaw10] (see pathway homospermidine biosynthesis).
About This Pathway
This spermidine biosynthetic pathway is based on both bioinformatic and genetic analysis [Lee09a, Hanfrey11]. In this pathway Vibrio cholerae is thought to utilize putrescine derived from either pathway putrescine biosynthesis I or putrescine biosynthesis III [Lee09a]. Campylobacter jejuni was shown to utilize putrescine derived from pathway putrescine biosynthesis II [Hanfrey11].
Some bacteria lack orthologs for the spermidine biosynthetic enzymes S-adenosylmethionine decarboxylase (EC 220.127.116.11) and spermidine synthase (EC 18.104.22.168) (see pathway spermidine biosynthesis I). Instead, Vibrio cholerae was shown to possess carboxynorspermidine/carboxyspermidine dehydrogenase (CANSDH) and carboxynorspermidine/carboxyspermidine decarboxylase (CANSDC). A clustered pair of genes encoding CANSDH and CANSDC was found to be widespread in the α-, β-, γ-, δ- and ε-proteobacteria, firmicutes and a candidate division TG-1, suggesting that this pathway for spermidine biosynthesis may be widely used. In Vibrio cholerae these enzymes were shown to be utilized for the biosynthesis of both spermidine (this pathway) and norspermidine (see pathway norspermidine biosynthesis) [Lee09a].
In Campylobacter jejuni however, the CANSDH and CANSDC orthologs were identified as carboxyspermidine dehydrogenase (CASDH) and carboxyspermidine decarboxylase (CASDC). spermidine was the only polyamine found in this organism, leading to the conclusion that Campylobacter jejuni does not synthesize norspermidine. Orthologs of CASDH and CASDC were also identified in many other bacterial phyla which include important human pathogens, human gut microbiome species, and deep sea hydrothermal vent species. These orthologs were often found to be clustered with putrescine biosynthetic genes, which also suggests their role in spermidine biosynthesis rather than norspermidine biosynthesis [Hanfrey11].
It was shown that in Campylobacter jejuni, CASDC activity is critical for growth. It was also shown that the function provided by spermidine in cell proliferation can be replaced by sym-homospermidine (or to a lesser extent norspermidine). Deletion mutants of all except one enzyme in the pathway abolished spermidine biosynthesis. The exception was CASDH, which showed a large accumulation of spermidine. It was suggested that a metabolic bypass was operative and that CASDH is a rate-limiting enzyme that regulates spermidine levels. It was also noted that the multiple spermidine biosynthetic pathways found in bacteria offer an opportunity for antimicrobial drug development [Hanfrey11].
Superpathways: superpathway of polyamine biosynthesis III
Hanfrey11: Hanfrey CC, Pearson BM, Hazeldine S, Lee J, Gaskin DJ, Woster PM, Phillips MA, Michael AJ (2011). "Alternative spermidine biosynthetic route is critical for growth of Campylobacter jejuni and is the dominant polyamine pathway in human gut microbiota." J Biol Chem 286(50);43301-12. PMID: 22025614
Lee09a: Lee J, Sperandio V, Frantz DE, Longgood J, Camilli A, Phillips MA, Michael AJ (2009). "An alternative polyamine biosynthetic pathway is widespread in bacteria and essential for biofilm formation in Vibrio cholerae." J Biol Chem 284(15);9899-907. PMID: 19196710
Morimoto10: Morimoto N, Fukuda W, Nakajima N, Masuda T, Terui Y, Kanai T, Oshima T, Imanaka T, Fujiwara S (2010). "Dual biosynthesis pathway for longer-chain polyamines in the hyperthermophilic archaeon Thermococcus kodakarensis." J Bacteriol 192(19);4991-5001. PMID: 20675472
Ohnuma05: Ohnuma M, Terui Y, Tamakoshi M, Mitome H, Niitsu M, Samejima K, Kawashima E, Oshima T (2005). "N1-aminopropylagmatine, a new polyamine produced as a key intermediate in polyamine biosynthesis of an extreme thermophile, Thermus thermophilus." J Biol Chem 280(34);30073-82. PMID: 15983049
Shaw10: Shaw FL, Elliott KA, Kinch LN, Fuell C, Phillips MA, Michael AJ (2010). "Evolution and multifarious horizontal transfer of an alternative biosynthetic pathway for the alternative polyamine sym-homospermidine." J Biol Chem 285(19);14711-23. PMID: 20194510
Alvarez04: Alvarez E, Ramon F, Magan C, Diez E (2004). "L-cystine inhibits aspartate-beta-semialdehyde dehydrogenase by covalently binding to the essential 135Cys of the enzyme." Biochim Biophys Acta 1696(1);23-9. PMID: 14726201
Angeles90: Angeles TS, Viola RE (1990). "The kinetic mechanisms of the bifunctional enzyme aspartokinase-homoserine dehydrogenase I from Escherichia coli." Arch Biochem Biophys 283(1);96-101. PMID: 2241177
Bearer78: Bearer CF, Neet KE (1978). "Threonine inhibition of the aspartokinase--homoserine dehydrogenase I of Escherichia coli. A slow transient and cooperativity of inhibition of the aspartokinase activity." Biochemistry 1978;17(17);3523-30. PMID: 28752
Biellmann80: Biellmann JF, Eid P, Hirth C (1980). "Affinity labeling of the Escherichia coli aspartate-beta-semialdehyde dehydrogenase with an alkylating coenzyme analogue. Half-site reactivity and competition with the substrate alkylating analogue." Eur J Biochem 1980;104(1);65-9. PMID: 6102911
Blanco03: Blanco J, Moore RA, Kabaleeswaran V, Viola RE (2003). "A structural basis for the mechanism of aspartate-beta-semialdehyde dehydrogenase from Vibrio cholerae." Protein Sci 12(1);27-33. PMID: 12493825
Broglie83: Broglie KE, Takahashi M (1983). "Fluorescence studies of threonine-promoted conformational transitions in aspartokinase I using the substrate analogue 2'(3')-O-(2,4,6-trinitrophenyl)adenosine 5'-triphosphate." J Biol Chem 1983;258(21);12940-6. PMID: 6313682
Chen93a: Chen NY, Jiang SQ, Klein DA, Paulus H (1993). "Organization and nucleotide sequence of the Bacillus subtilis diaminopimelate operon, a cluster of genes encoding the first three enzymes of diaminopimelate synthesis and dipicolinate synthase." J Biol Chem 268(13);9448-65. PMID: 8098035
Deng10: Deng X, Lee J, Michael AJ, Tomchick DR, Goldsmith EJ, Phillips MA (2010). "Evolution of substrate specificity within a diverse family of beta/alpha-barrel-fold basic amino acid decarboxylases: X-ray structure determination of enzymes with specificity for L-arginine and carboxynorspermidine." J Biol Chem 285(33);25708-19. PMID: 20534592
FalcozKelly69: Falcoz-Kelly F, van Rapenbusch R, Cohen GN (1969). "The methionine-repressible homoserine dehydrogenase and aspartokinase activities of Escherichia coli K 12. Preparation of the homogeneous protein catalyzing the two activities. Molecular weight of the native enzyme and of its subunits." Eur J Biochem 8(1);146-52. PMID: 4889171
James02: James CL, Viola RE (2002). "Production and characterization of bifunctional enzymes. Domain swapping to produce new bifunctional enzymes in the aspartate pathway." Biochemistry 41(11);3720-5. PMID: 11888289
Jullien88: Jullien M, Baudet S, Rodier F, Le Bras G (1988). "Allosteric transition of aspartokinase I-homoserine dehydrogenase I studied by time-resolved fluorescence." Biochimie 1988;70(12);1807-14. PMID: 3150686
Kalinowski91: Kalinowski J, Cremer J, Bachmann B, Eggeling L, Sahm H, Puhler A (1991). "Genetic and biochemical analysis of the aspartokinase from Corynebacterium glutamicum." Mol Microbiol 5(5);1197-204. PMID: 1956296
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