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 → Fatty Acid and Lipid Biosynthesis → Sterol Biosynthesis|
Some taxa known to possess this pathway include : Gemmata obscuriglobus, Homo sapiens, Methylococcus capsulatus, Methylosphaera hansonii, Nannocystis exedens, Saccharomyces cerevisiae, Stigmatella aurantiaca
Sterols are ubiquitous components of eukaryotes that play a key role in controlling fluidity and flexibility of their cell membranes. lanosterol is a tetracyclic triterpenoid, which is the compound from which all sterols are derived.
Lanosterol is found in vertebrates and fungi, where it is an intermediate in the synthesis of cholesterol and ergosterol, respectively. In addition, lanosterol has been found in several prokaryotes, including the Myxococcales species Stigmatella aurantiaca [Bode03] and Nannocystis exedens [Kohl83], Gemmata obscuriglobus [Pearson03], and Methylosphaera hansonii [Schouten00].
The enzyme that catalyzes the conversion of (3S)-2,3-epoxy-2,3-dihydrosqualene to lanosterol is lanosterol synthase, also known as 2,3-oxidosqualene-lanosterol cyclase. The polycyclization cascade of (3S)-2,3-epoxy-2,3-dihydrosqualene is one of the most complicated biochemical reactions catalyzed by a single protein. It leads to the formation of new carbon-carbon bonds with accurate regio- and stereochemical specificities [Hoshino02, Yoder05].
A prokaryotic enzyme has recently been cloned from Methylococcus capsulatus and expressed in Escherichia coli, confirming activity [Nakano07]. The enzymatic reaction proceeded in a regio- and stereospecific fashion identical to those from eukaryotic species, implying that the bacterial gene may have been acquired from ancient eukaryotes (along with the gene encoding squalene monooxygenase) through lateral gene transfer [Nakano07].
Superpathways: superpathway of ergosterol biosynthesis I, cholesterol biosynthesis III (via desmosterol), cholesterol biosynthesis II (via 24,25-dihydrolanosterol), cholesterol biosynthesis I, superpathway of cholesterol biosynthesis
Bode03: Bode HB, Zeggel B, Silakowski B, Wenzel SC, Reichenbach H, Muller R (2003). "Steroid biosynthesis in prokaryotes: identification of myxobacterial steroids and cloning of the first bacterial 2,3(S)-oxidosqualene cyclase from the myxobacterium Stigmatella aurantiaca." Mol Microbiol 47(2);471-81. PMID: 12519197
Nakano07: Nakano C, Motegi A, Sato T, Onodera M, Hoshino T (2007). "Sterol Biosynthesis by a Prokaryote: First in Vitro Identification of the Genes Encoding Squalene Epoxidase and Lanosterol Synthase from Methylococcus capsulatus." Biosci Biotechnol Biochem 71(10);2543-50. PMID: 17928701
Pearson03: Pearson A, Budin M, Brocks JJ (2003). "Phylogenetic and biochemical evidence for sterol synthesis in the bacterium Gemmata obscuriglobus." Proc Natl Acad Sci U S A 100(26);15352-7. PMID: 14660793
Baker95a: Baker CH, Matsuda SP, Liu DR, Corey EJ (1995). "Molecular cloning of the human gene encoding lanosterol synthase from a liver cDNA library." Biochem Biophys Res Commun 213(1);154-60. PMID: 7639730
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
Corey94: Corey EJ, Matsuda SP, Bartel B (1994). "Molecular cloning, characterization, and overexpression of ERG7, the Saccharomyces cerevisiae gene encoding lanosterol synthase." Proc Natl Acad Sci U S A 91(6);2211-5. PMID: 8134375
Hattori00: Hattori M, Fujiyama A, Taylor TD, Watanabe H, Yada T, Park HS, Toyoda A, Ishii K, Totoki Y, Choi DK, Groner Y, Soeda E, Ohki M, Takagi T, Sakaki Y, Taudien S, Blechschmidt K, Polley A, Menzel U, Delabar J, Kumpf K, Lehmann R, Patterson D, Reichwald K, Rump A, Schillhabel M, Schudy A, Zimmermann W, Rosenthal A, Kudoh J, Schibuya K, Kawasaki K, Asakawa S, Shintani A, Sasaki T, Nagamine K, Mitsuyama S, Antonarakis SE, Minoshima S, Shimizu N, Nordsiek G, Hornischer K, Brant P, Scharfe M, Schon O, Desario A, Reichelt J, Kauer G, Blocker H, Ramser J, Beck A, Klages S, Hennig S, Riesselmann L, Dagand E, Haaf T, Wehrmeyer S, Borzym K, Gardiner K, Nizetic D, Francis F, Lehrach H, Reinhardt R, Yaspo ML, (2000). "The DNA sequence of human chromosome 21." Nature 405(6784);311-9. PMID: 10830953
Milla02: Milla P, Athenstaedt K, Viola F, Oliaro-Bosso S, Kohlwein SD, Daum G, Balliano G (2002). "Yeast oxidosqualene cyclase (Erg7p) is a major component of lipid particles." J Biol Chem 277(4);2406-12. PMID: 11706015
Mo03: Mo C, Milla P, Athenstaedt K, Ott R, Balliano G, Daum G, Bard M (2003). "In yeast sterol biosynthesis the 3-keto reductase protein (Erg27p) is required for oxidosqualene cyclase (Erg7p) activity." Biochim Biophys Acta 1633(1);68-74. PMID: 12842197
Reinhart87: Reinhart MP, Billheimer JT, Faust JR, Gaylor JL (1987). "Subcellular localization of the enzymes of cholesterol biosynthesis and metabolism in rat liver." J Biol Chem 262(20);9649-55. PMID: 3597431
Ruf04: Ruf A, Muller F, D'Arcy B, Stihle M, Kusznir E, Handschin C, Morand OH, Thoma R (2004). "The monotopic membrane protein human oxidosqualene cyclase is active as monomer." Biochem Biophys Res Commun 315(2);247-54. PMID: 14766201
Thoma04: Thoma R, Schulz-Gasch T, D'Arcy B, Benz J, Aebi J, Dehmlow H, Hennig M, Stihle M, Ruf A (2004). "Insight into steroid scaffold formation from the structure of human oxidosqualene cyclase." Nature 432(7013);118-22. PMID: 15525992
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