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MetaCyc Pathway: superpathway of ergosterol biosynthesis I
Traceable author statement to experimental support

Pathway diagram: superpathway of ergosterol biosynthesis I

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: superpathway of ergosterol biosynthesis I (fungi)

Superclasses: BiosynthesisFatty Acid and Lipid BiosynthesisSterol BiosynthesisErgosterol Biosynthesis

Some taxa known to possess this pathway include : Saccharomyces cerevisiae

Expected Taxonomic Range: Fungi

ergosterol is a major constituent of the fungal plasma membrane [Paltauf92, Parks95]. Only the very last part of this pathway (starting at zymosterol) is fungal-specific. Most of the pathway is shared between yeast and other organisms whose plasma membranes are composed predominantly of other types of sterols, (e.g. cholesterol).

This superpathway describes the complete pathway for the synthesis of ergosterol from the central metabolite acetyl-CoA. It includes several subpathways, including the mevalonate pathway I, which describes the synthesis of the isopreoid building blocks dimethylallyl diphosphate and isopentenyl diphosphate, trans, trans-farnesyl diphosphate biosynthesis, which describes the synthesis of this central intermediate, which feeds into many different metabolic routes, epoxysqualene biosynthesis, which describes the first committed step for the synthesis of sterols, generating (3S)-2,3-epoxy-2,3-dihydrosqualene, and finally the pathways for zymosterol biosynthesis and ergosterol biosynthesis I.

In Saccharomyces cerevisiae, some of the steps in the pathway are essential for viability [Bard93]. As a result, this pathway has been the subject of intensive investigation as a target of antifungal drugs [Lupetti02]. The major target of azole antifungal drugs is cytochrome P450 51, a member of the cytochrome P450 family encoded by the gene ERG11. The specific target of allylamine drugs such as terbinafine (known as Lamisil) is squalene monooxygenase, encoded by the ERG1 gene [Leber03]. Mutations in the genes encoding these enzymes and others in the pathway, as well as alterations in the expression levels of the pathway constituents, can lead to antifungal drug resistance [Lupetti02].

Even though the pathway is very common in fungi, it is not universally present; for example, Pneumocystis carinii plasma membranes lack ergosterol [Kaneshiro02].

Subpathways: lanosterol biosynthesis, mevalonate pathway I, trans, trans-farnesyl diphosphate biosynthesis, ergosterol biosynthesis I, zymosterol biosynthesis, epoxysqualene biosynthesis

Variants: ergosterol biosynthesis II, superpathway of ergosterol biosynthesis II

Created 21-Dec-2004 by Hong E, Saccharomyces Genome Database
Revised 30-Oct-2008 by Caspi R, SRI International


Bard93: Bard M, Lees ND, Turi T, Craft D, Cofrin L, Barbuch R, Koegel C, Loper JC (1993). "Sterol synthesis and viability of erg11 (cytochrome P450 lanosterol demethylase) mutations in Saccharomyces cerevisiae and Candida albicans." Lipids 28(11);963-7. PMID: 8277826

Kaneshiro02: Kaneshiro ES (2002). "Sterol biosynthesis in Pneumocystis: unique steps that define unique targets." Drug Resist Updat 5(6);259-68. PMID: 12531182

Leber03: Leber R, Fuchsbichler S, Klobucnikova V, Schweighofer N, Pitters E, Wohlfarter K, Lederer M, Landl K, Ruckenstuhl C, Hapala I, Turnowsky F (2003). "Molecular mechanism of terbinafine resistance in Saccharomyces cerevisiae." Antimicrob Agents Chemother 47(12);3890-900. PMID: 14638499

Lupetti02: Lupetti A, Danesi R, Campa M, Del Tacca M, Kelly S (2002). "Molecular basis of resistance to azole antifungals." Trends Mol Med 8(2);76-81. PMID: 11815273

Paltauf92: Paltauf, F, Kohlwein, S, Henry, SA (1992). "Regulation and compartmentalization of lipid synthesis in yeast." The Molecular and Cellular Biology of the yeastSaccharomyces: Gene Expression, Vol. 2, pp.415 - 500.

Parks95: Parks LW, Casey WM (1995). "Physiological implications of sterol biosynthesis in yeast." Annu Rev Microbiol 49;95-116. PMID: 8561481

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

Abe94: Abe I, Tomesch JC, Wattanasin S, Prestwich GD (1994). "Inhibitors of squalene biosynthesis and metabolism." Nat Prod Rep 11(3);279-302. PMID: 15200015

Aharoni03: Aharoni A, Giri AP, Deuerlein S, Griepink F, de Kogel WJ, Verstappen FW, Verhoeven HA, Jongsma MA, Schwab W, Bouwmeester HJ (2003). "Terpenoid metabolism in wild-type and transgenic Arabidopsis plants." Plant Cell 15(12);2866-84. PMID: 14630967

Alber06: Alber BE, Spanheimer R, Ebenau-Jehle C, Fuchs G (2006). "Study of an alternate glyoxylate cycle for acetate assimilation by Rhodobacter sphaeroides." Mol Microbiol 61(2);297-309. PMID: 16856937

Anderson89: Anderson MS, Muehlbacher M, Street IP, Proffitt J, Poulter CD (1989). "Isopentenyl diphosphate:dimethylallyl diphosphate isomerase. An improved purification of the enzyme and isolation of the gene from Saccharomyces cerevisiae." J Biol Chem 1989;264(32);19169-75. PMID: 2681212

Anderson89a: Anderson MS, Yarger JG, Burck CL, Poulter CD (1989). "Farnesyl diphosphate synthetase. Molecular cloning, sequence, and expression of an essential gene from Saccharomyces cerevisiae." J Biol Chem 1989;264(32);19176-84. PMID: 2681213

Aoyama83: Aoyama Y, Yoshida Y, Hata S, Nishino T, Katsuki H (1983). "Buthiobate: a potent inhibitor for yeast cytochrome P-450 catalyzing 14 alpha-demethylation of lanosterol." Biochem Biophys Res Commun 115(2);642-7. PMID: 6414474

Aoyama96: Aoyama Y, Noshiro M, Gotoh O, Imaoka S, Funae Y, Kurosawa N, Horiuchi T, Yoshida Y (1996). "Sterol 14-demethylase P450 (P45014DM*) is one of the most ancient and conserved P450 species." J Biochem (Tokyo) 119(5);926-33. PMID: 8797093

Arthington91: Arthington BA, Bennett LG, Skatrud PL, Guynn CJ, Barbuch RJ, Ulbright CE, Bard M (1991). "Cloning, disruption and sequence of the gene encoding yeast C-5 sterol desaturase." Gene 102(1);39-44. PMID: 1864507

Arthington91a: Arthington BA, Hoskins J, Skatrud PL, Bard M (1991). "Nucleotide sequence of the gene encoding yeast C-8 sterol isomerase." Gene 107(1);173-4. PMID: 1743517

Ashman91: Ashman WH, Barbuch RJ, Ulbright CE, Jarrett HW, Bard M (1991). "Cloning and disruption of the yeast C-8 sterol isomerase gene." Lipids 26(8);628-32. PMID: 1779709

Bairoch93a: Bairoch A, Boeckmann B (1993). "The SWISS-PROT protein sequence data bank, recent developments." Nucleic Acids Res. 21:3093-3096. PMID: 8332529

Balliano92: Balliano G, Viola F, Ceruti M, Cattel L (1992). "Characterization and partial purification of squalene-2,3-oxide cyclase from Saccharomyces cerevisiae." Arch Biochem Biophys 293(1);122-9. PMID: 1731628

Bard72: Bard M (1972). "Biochemical and genetic aspects of nystatin resistance in saccharomyces cerevisiae." J Bacteriol 111(3);649-57. PMID: 4559817

Bard81: Bard M, Downing JF (1981). "Genetic and biochemical aspects of yeast sterol regulation involving 3-hydroxy-3-methylglutaryl coenzyme A reductase." J Gen Microbiol 1981;125(Pt 2);415-20. PMID: 7033470

Bard96: Bard M, Bruner DA, Pierson CA, Lees ND, Biermann B, Frye L, Koegel C, Barbuch R (1996). "Cloning and characterization of ERG25, the Saccharomyces cerevisiae gene encoding C-4 sterol methyl oxidase." Proc Natl Acad Sci U S A 93(1);186-90. PMID: 8552601

Barker82: Barker HA, Kahn JM, Hedrick L (1982). "Pathway of lysine degradation in Fusobacterium nucleatum." J Bacteriol 152(1);201-7. PMID: 6811551

Barnard81: Barnard GF, Popjak G (1981). "Human liver prenyltransferase and its characterization." Biochim Biophys Acta 661(1);87-99. PMID: 7295734

Basson86: Basson ME, Thorsness M, Rine J (1986). "Saccharomyces cerevisiae contains two functional genes encoding 3-hydroxy-3-methylglutaryl-coenzyme A reductase." Proc Natl Acad Sci U S A 1986;83(15);5563-7. PMID: 3526336

Berg07: Berg IA, Kockelkorn D, Buckel W, Fuchs G (2007). "A 3-hydroxypropionate/4-hydroxybutyrate autotrophic carbon dioxide assimilation pathway in Archaea." Science 318(5857);1782-6. PMID: 18079405

Berges97: Berges T, Guyonnet D, Karst F (1997). "The Saccharomyces cerevisiae mevalonate diphosphate decarboxylase is essential for viability, and a single Leu-to-Pro mutation in a conserved sequence leads to thermosensitivity." J Bacteriol 1997;179(15);4664-70. PMID: 9244250

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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
Page generated by Pathway Tools version 19.5 (software by SRI International) on Fri Apr 29, 2016, biocyc14.