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Legend for Pathway Diagram
If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Synonyms: ornithine spermine biosynthesis
| Superclasses: | Biosynthesis -> Amines and Polyamines Biosynthesis |
Summary:
An intact polyamine biosynthesis pathway is required for wild-type growth of C.
albicans and C. tropicalis, as treatment with compounds that decrease
polyamine biosynthesis (by inhibition of either ornithine decarboxylase or spermidine
synthase) results in growth inhibition [
Pfaller88
]. Polyamines stimulate adenylate
cyclase, which in turn affects hyphal formation; inhibition of ornithine decarboxylase is
observed to decrease C. albicans filamentation under conditions that normally
promote hyphal growth. [
Ueno04
,
Martinez90
]. In Mucorales, inhibition of
polyamine biosynthesis has also been observed to impair germ tube formation and other
forms of fungal differentiation, and this impairment can be alleviated by treatment with
inhibitors of DNA methylation [
RuizHerrer94
].
Ornithine decarboxylase (ODC), encoded by the SPE1 gene, has been subject to functional characterization in C. albicans [ Lopez97 , McNemar97 ]. Enzyme activity is induced upon initiation of hyphal growth, and this regulation appears to take place at a post-transcriptional level [ Lopez97 ]. In many eukaryotes, ornithine decarboxylase is subject to feedback regulation by polyamines, via inhibitors that bind to and induce proteasome-mediated degradation of the enzyme, and production of the inhibitors themselves is subject to regulation by ribosomal frameshifting [ Coffino , Mangold05 ]. While conserved widely among eukaryotes, including some fungi [ Coffino , Mangold05 ], this antizyme mechanism has not been noted to exist in C. albicans as of 2007.
C. albicans has orthologs of the S. cerevisiae genes that encode S-adenosylmethionine decarboxylase (SPE2/orf19.568) and spermidine synthase (orf19.2250) [ Remm01 ]. An activity that is likely due to spermine synthase has also been observed in C. albicans [ Hamana89 ], and, while not meeting the criteria to be termed an "ortholog" in CGD, orf19.4960 is closely related in sequence to S. cerevisiae SPE4, which encodes this enzyme.
Citations: [ HamasakiKa98 , Herrero99 , White01 , Bezjak90 ]
Variants: UDP-N-acetylglucosamine biosynthesis
Unification Links: YeastCyc:POLYAMSYN-YEAST-PWY
Bezjak90: Bezjak V, al-Nakib T, Chandy R, Verghese R (1990). "Cell-constituent polyamines in Candida species and new biotyping of Candida albicans, Candida tropicalis and Candida parapsilosis strains." J Med Vet Mycol 28(4);267-73. PMID: 2269908
Coffino: Coffino P "Antizyme, a mediator of ubiquitin-independent proteasomal degradation." Biochimie 83(3-4);319-23. PMID: 11295492
Hamana89: Hamana K, Matsuzaki S, Hosaka K, Yamashita S (1989). "Interconversion of polyamines in wild-type strains and mutants of yeasts and the effects of polyamines on their growth." FEMS Microbiol Lett 52(1-2);231-6. PMID: 2689281
HamasakiKa98: Hamasaki-Katagiri N, Katagiri Y, Tabor CW, Tabor H (1998). "Spermine is not essential for growth of Saccharomyces cerevisiae: identification of the SPE4 gene (spermine synthase) and characterization of a spe4 deletion mutant." Gene 210(2);195-201. PMID: 9573363
Herrero99: Herrero AB, Lopez MC, Garcia S, Schmidt A, Spaltmann F, Ruiz-Herrera J, Dominguez A (1999). "Control of filament formation in Candida albicans by polyamine levels." Infect Immun 67(9);4870-8. PMID: 10456943
Lopez97: Lopez MC, Garcia S, Ruiz-Herrera J, Dominguez A (1997). "The ornithine decarboxylase gene from Candida albicans. Sequence analysis and expression during dimorphism." Curr Genet 32(2);108-14. PMID: 9294258
Mangold05: Mangold U (2005). "The antizyme family: polyamines and beyond." IUBMB Life 57(10);671-6. PMID: 16223706
Martinez90: Martinez JP, Lopez-Ribot JL, Gil ML, Sentandreu R, Ruiz-Herrera J (1990). "Inhibition of the dimorphic transition of Candida albicans by the ornithine decarboxylase inhibitor 1,4-diaminobutanone: alterations in the glycoprotein composition of the cell wall." J Gen Microbiol 136(10);1937-43. PMID: 2269870
McNemar97: McNemar MD, Gorman JA, Buckley HR (1997). "Isolation and sequence of the gene encoding ornithine decarboxylase, SPE1, from Candida albicans by complementation of a spe1 delta strain of Saccharomyces cerevisiae." Yeast 13(14);1383-9. PMID: 9392083
Pfaller88: Pfaller MA, Riley J, Gerarden T (1988). "Polyamine depletion and growth inhibition in Candida albicans and Candida tropicalis by alpha-difluoromethylornithine and cyclohexylamine." J Med Vet Mycol 26(2);119-26. PMID: 3138402
Remm01: Remm M, Storm CE, Sonnhammer EL (2001). "Automatic clustering of orthologs and in-paralogs from pairwise species comparisons." J Mol Biol 314(5);1041-52. PMID: 11743721
RuizHerrer94: Ruiz-Herrera J (1994). "Polyamines, DNA methylation, and fungal differentiation." Crit Rev Microbiol 20(2);143-50. PMID: 8080626
Ueno04: Ueno Y, Fukumatsu M, Ogasawara A, Watanabe T, Mikami T, Matsumoto T (2004). "Hyphae formation of Candida albicans is regulated by polyamines." Biol Pharm Bull 27(6);890-2. PMID: 15187439
White01: White WH, Gunyuzlu PL, Toyn JH (2001). "Saccharomyces cerevisiae is capable of de Novo pantothenic acid biosynthesis involving a novel pathway of beta-alanine production from spermine." J Biol Chem 276(14);10794-800. PMID: 11154694
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