C. albicans Pathway: tyrosol biosynthesis

Legend for Pathway Diagram

If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Synonyms: tyrosine degradation

Summary:
Tyrosol (2,4-(hydroxyphenyl)-ethanol) is a quorum-sensing molecule that is secreted by Candida albicans; it acts to stimulate growth under dilute culture conditions ("lag phase" growth) [ Chen04 ]. Tyrosol also stimulates germ tube formation [ Chen04 ] and has a protective effect against human phagocytic cells [ Cremer99 ]. When both farnesol and tyrosol are present, the morphogenetic effect of farnesol is dominant; inhibition of germ tube formation is observed (see [ Kruppa08 ]).

Aromatic alcohol production, of phenethyl alcohol, tyrosol, and tryptophol from phenylalanine, tyrosine, or tryptophan, respectively, has been demonstrated in C. albicans, and homology and similar gene regulation of ARO8, ARO9, and ARO10 suggests that this organism, like S. cerevisiae, utilizes the Ehrlich pathway for biosynthesis of these fusel oils [ Ghosh08 ]. Aromatic alcohol biosynthesis is induced under anaerobic conditions compared to aerobic conditions, is significantly enhanced by the presence of precursor compounds (phenylalanine, tyrosine, or tryptophan) in the growth media, and is reduced in the presence of ammonia (even in the presence of other nitrogen sources) [ Ghosh08 ]. The amount of biosynthesis of aromatic alcohols does not show any large difference between growth at 30 or 37 deg [ Ghosh08 ]. Tyrosol production is enhanced in biofilms compared to planktonic culture [ Alem06 ].

Tyrosine is described as the "presumptive precursor" in tyrosol biosynthesis in Candida [ Chen04 ].

C. albicans ARO8 and ARO9 are orthologous to S. cerevisiae ARO8 and ARO9, respectively [ Remm01 ].

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Tyrosine degradation, pathway comment from Saccharomyces Genome Database: While Saccharomyces cerevisiae can use most amino acids as their sole nitrogen source, they can only use a few amino acids as a carbon source to support growth [ Large86 , Cooper82 ]. This is in contrast to most eukaryotes and some fungi, which can metabolize amino acids completely, utilizing them as sole sources of carbon and nitrogen [ Stryer88 , Large86 ]. S. cerevisiae degrade the aromatic amino acids (tyrosine, phenylalanine, and tryptophan) and branched-chain amino acids (valine, leucine, and iso-leucine) via the Ehrlich pathway [ Sentheshan60 , Dickinson00 ]. This pathway is comprised of the following steps: 1) deamination of the amino acid to the corresponding alpha-keto acid; 2) decarboxylation of the resulting alpha-keto acid to the respective aldehyde; and, 3) reduction of the aldehyde to form the corresponding long chain or complex alcohol, known as a fusel alcohol or fusel oil [ Dickinson00 , Large86 ]. Fusel alcohols are important flavor and aroma compounds in yeast-fermented food products and beverages (as reported in [ terSchure98 ].

Both the constitutive aromatic aminotransferase I (ARO8p) and the inducible aromatic aminotransferase II (ARO9p) can catalyze the initial reaction in tyrosine degradation [ Kradolfer82 ]. In vitro studies demonstrated that Aro9p is active with phenylpyruvate, pyruvate, or p-hydroxyphenylpyruvate, but not 2-oxoglutarate as the amino acceptor, while Aro8p is active with phenylpyruvate, pyruvate, or 2-oxoglutarate [ Kradolfer82 ]. Aro9p is induced by aromatic amino acids and is subject to nitrogen regulation [ Kradolfer82 , Iraqui99 ].

Citations: [ SENTHESHAN60 , SENTHESHAN58 , Urrestaraz98 , Iraqui98 , Blankenshi06 , Nickerson06 , Hogan06 ]

Unification Links: YeastCyc:PWY3O-4108

Pathway Evidence Glyph:

Key to pathway glyph edge colors:

References

Alem06: Alem MA, Oteef MD, Flowers TH, Douglas LJ (2006). "Production of tyrosol by Candida albicans biofilms and its role in quorum sensing and biofilm development." Eukaryot Cell 5(10);1770-9. PMID: 16980403

Blankenshi06: Blankenship JR, Mitchell AP (2006). "How to build a biofilm: a fungal perspective." Curr Opin Microbiol 9(6);588-94. PMID: 17055772

Chen04: Chen H, Fujita M, Feng Q, Clardy J, Fink GR (2004). "Tyrosol is a quorum-sensing molecule in Candida albicans." Proc Natl Acad Sci U S A 101(14);5048-52. PMID: 15051880

Cooper82: Cooper, TG (1982). "Nitrogen Metabolism in Saccharomyces cerevisiae." In: Strathern JN, Jones EW, Broach JR (eds) The Molecular Biology of the Yeast Saccharomyces, Metabolism and Gene Expression. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, pp 39-99.

Cremer99: Cremer J, Vatou V, Braveny I (1999). "2,4-(hydroxyphenyl)-ethanol, an antioxidative agent produced by Candida spp., impairs neutrophilic yeast killing in vitro." FEMS Microbiol Lett 170(2);319-25. PMID: 9933927

Dickinson00: Dickinson JR (2000). "Pathways of leucine and valine catabolism in yeast." Methods Enzymol 324;80-92. PMID: 10989420

Ghosh08: Ghosh S, Kebaara BW, Atkin AL, Nickerson KW (2008). "Regulation of aromatic alcohol production in Candida albicans." Appl Environ Microbiol NIL. PMID: 18836025

Hogan06: Hogan DA (2006). "Talking to themselves: autoregulation and quorum sensing in fungi." Eukaryot Cell 5(4);613-9. PMID: 16607008

Iraqui98: Iraqui I, Vissers S, Cartiaux M, Urrestarazu A (1998). "Characterisation of Saccharomyces cerevisiae ARO8 and ARO9 genes encoding aromatic aminotransferases I and II reveals a new aminotransferase subfamily." Mol Gen Genet 257(2);238-48. PMID: 9491083

Iraqui99: Iraqui I, Vissers S, Andre B, Urrestarazu A (1999). "Transcriptional induction by aromatic amino acids in Saccharomyces cerevisiae." Mol Cell Biol 19(5);3360-71. PMID: 10207060

Kradolfer82: Kradolfer P, Niederberger P, Hutter R (1982). "Tryptophan degradation in Saccharomyces cerevisiae: characterization of two aromatic aminotransferases." Arch Microbiol 133(3);242-8. PMID: 6763508

Kruppa08: Kruppa M (2008). "Quorum sensing and Candida albicans." Mycoses NIL. PMID: 18983434

Large86: Large PJ (1986). "Degradation of Organic Nitrogen Compounds by Yeasts." Yeast (2) 1-34.

Nickerson06: Nickerson KW, Atkin AL, Hornby JM (2006). "Quorum sensing in dimorphic fungi: farnesol and beyond." Appl Environ Microbiol 72(6);3805-13. PMID: 16751484

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

SENTHESHAN58: SENTHESHANMUGANATHAN S, ELSDEN SR (1958). "The mechanism of the formation of tyrosol by Saccharomyces cerevisiae." Biochem J 69(2);210-8. PMID: 13546168

SENTHESHAN60: SENTHESHANMUGANATHAN S (1960). "The purification and properties of the tyrosine-2-oxoglutarate transaminase of Saccharomyces cerevisiae." Biochem J 77;619-25. PMID: 13750129

Sentheshan60: Sentheshanmuganathan S (1960). "The mechanism of the formation of higher alcohols from amino acids by Saccharomyces cerevisiae." Biochem J. 74:568-576.

Stryer88: Stryer L "Biochemistry." WH Freeman and Co., 3rd edition, New York, 1988.

terSchure98: ter Schure EG, Flikweert MT, van Dijken JP, Pronk JT, Verrips CT (1998). "Pyruvate decarboxylase catalyzes decarboxylation of branched-chain 2-oxo acids but is not essential for fusel alcohol production by Saccharomyces cerevisiae." Appl Environ Microbiol 64(4);1303-7. PMID: 9546164

Urrestaraz98: Urrestarazu A, Vissers S, Iraqui I, Grenson M (1998). "Phenylalanine- and tyrosine-auxotrophic mutants of Saccharomyces cerevisiae impaired in transamination." Mol Gen Genet 257(2);230-7. PMID: 9491082

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