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MetaCyc Pathway: norspermidine biosynthesis
Inferred from experiment

Enzyme View:

Pathway diagram: norspermidine biosynthesis

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.

Synonyms: sym-norspermidine biosynthesis

Superclasses: BiosynthesisAmines and Polyamines Biosynthesis

Some taxa known to possess this pathway include : Vibrio alginolyticus, Vibrio alginolyticus NBRC 15630 = ATCC 17749, Vibrio cholerae, Vibrio parahaemolyticus, Vibrio vulnificus, Vibrio vulnificus CMCP6

Expected Taxonomic Range: Vibrionaceae

General Background

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]). Links to their biosynthetic pathways can be found by clicking on these compounds links. See also superpathway of polyamine biosynthesis I, superpathway of polyamine biosynthesis II and superpathway of polyamine biosynthesis III. In members of the genus Vibrio, norspermidine is a major polyamine (in [Lee09a].

About This Pathway

In this pathway L-aspartate-semialdehyde donates a carboxyaminopropyl group to propane-1,3-diamine to form carboxynorspermidine in a reaction catalyzed by carboxynorspermidine/carboxyspermidine dehydrogenase (CANSDH). Decarboxylation of carboxynorspermidine catalyzed by carboxynorspermidine/carboxyspermidine decarboxylase (CANSDC) produces norspermidine. L-aspartate-semialdehyde is also a precursor for propane-1,3-diamine biosynthesis from L-2,4-diaminobutanoate which is catalyzed by a bifunctional fusion protein L-2,4-diaminobutyrate aminotransferase/decarboxylase (DABA AT/DC) ( [Yamamoto86, Lee09a] and in [Shaw10]).

This L-aspartate-semialdehyde based pathway has been experimentally demonstrated in vivo in Vibrio cholerae including a branch of this pathway that leads to the biosynthesis of spermidine as shown in the pathway link. Both pathways are shown together in superpathway of polyamine biosynthesis III.

Heterologous expression in Escherichia coli of the genes encoding the enzymes in this pathway resulted in accumulation of propane-1,3-diamine and norspermidine (which are inactive polyamines in Escherichia coli). Deletion of the gene encoding CANSDC in Vibrio cholerae resulted in accumulation of carboxynorspermidine. Deletion of the genes encoding either CANSDC or CANSDH led to loss of norspermidine and spermidine, thus identifying the gene encoding CANSDH. Interestingly, deletion of the Vibrio cholerae genes encoding either CANSDH or CANSDC reduced the growth rate of planktonic cells by approximately 50% and severely reduced biofilm formation. Biofilm formation could be rescued by adding exogenous norspermidine, but not spermidine . The pathway did not appear to be related to the infectivity of Vibrio cholerae, using a mouse model [Lee09a]. Earlier work also suggested a role for norspermidine in biofilm formation in Vibrio cholerae [Karatan05].

Bioinformatic analysis suggested that DABA AT/DC fusion proteins and their clustering with CANSDH and CANSDC were found only in the family Vibrionaceae, giving support to their role in both spermidine and norspermidine biosynthesis in these organisms. However, a clustered pair of CANSDH and CANSDC genes was widespread in the α-, β-, γ-, δ- and ε-proteobacteria, firmicutes and a candidate division TG-1, suggesting that the pathway for spermidine biosynthesis may be more widely used. However, this conclusion could not be extended to norspermidine biosynthesis without experimental support due to the use of L-2,4-diaminobutanoate in other pathways (see ectoine biosynthesis, pyoverdine I biosynthesis and rhizobactin 1021 biosynthesis) [Lee09a].

Superpathways: superpathway of polyamine biosynthesis III

Created 04-Aug-2010 by Fulcher CA, SRI International


Karatan05: Karatan E, Duncan TR, Watnick PI (2005). "NspS, a predicted polyamine sensor, mediates activation of Vibrio cholerae biofilm formation by norspermidine." J Bacteriol 187(21);7434-43. PMID: 16237027

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

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

Yamamoto86: Yamamoto S, Hamanaka K, Suemoto Y, Ono B, Shinoda S (1986). "Evidence for the presence of a novel biosynthetic pathway for norspermidine in Vibrio." Can J Microbiol 32(2);99-103. PMID: 3697846

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

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

BRENDA14: BRENDA team (2014). Imported from BRENDA version existing on Aug 2014.

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

Canovas98: Canovas D, Vargas C, Calderon MI, Ventosa A, Nieto JJ (1998). "Characterization of the genes for the biosynthesis of the compatible solute ectoine in the moderately halophilic bacterium Halomonas elongata DSM 3043." Syst Appl Microbiol 1998;21(4);487-97. PMID: 9924816

Chassagnole01: Chassagnole C, Rais B, Quentin E, Fell DA, Mazat JP (2001). "An integrated study of threonine-pathway enzyme kinetics in Escherichia coli." Biochem J 356(Pt 2);415-23. PMID: 11368768

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

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

Graves90: Graves LM, Switzer RL (1990). "Aspartokinase III, a new isozyme in Bacillus subtilis 168." J Bacteriol 172(1);218-23. PMID: 2152900

Hegeman70: Hegeman G, Cohen G, Morgan R "Aspartic semialdehyde dehydrogenase (Escherichia coli K12)." Methods in Enzymology 1970; 17A:708-713.

Helmward89: Helmward Z "Handbook of Enzyme Inhibitors. 2nd, revised and enlarged edition." Weinheim, Federal Republic of Germany ; New York, NY, USA , 1989.

Huang93: Huang KJ, Hseu TH (1993). "Effects of lysine-sensitive aspartokinase III on lysine biosynthesis in Escherichia coli K-12." Proc Natl Sci Counc Repub China B 17(3);91-7. PMID: 8290655

Ikai97: Ikai H, Yamamoto S (1997). "Identification and analysis of a gene encoding L-2,4-diaminobutyrate:2-ketoglutarate 4-aminotransferase involved in the 1,3-diaminopropane production pathway in Acinetobacter baumannii." J Bacteriol 179(16);5118-25. PMID: 9260954

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

Keng96: Keng YF, Viola RE (1996). "Specificity of aspartokinase III from Escherichia coli and an examination of important catalytic residues." Arch Biochem Biophys 335(1);73-81. PMID: 8914836

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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
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