Updated BioCyc iOS App now
available in iTunes store
Updated BioCyc iOS App now
available in iTunes store
Updated BioCyc iOS App now
available in iTunes store
Updated BioCyc iOS App now
available in iTunes store
Updated BioCyc iOS App now
available in iTunes store

MetaCyc Pathway: lanosterol biosynthesis
Inferred from experiment

Enzyme View:

Pathway diagram: lanosterol 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.

Superclasses: BiosynthesisFatty Acid and Lipid BiosynthesisSterol Biosynthesis

Some taxa known to possess this pathway include : Gemmata obscuriglobus, Homo sapiens, Methylococcus capsulatus, Methylosphaera hansonii, Nannocystis exedens, Saccharomyces cerevisiae, Stigmatella aurantiaca

Expected Taxonomic Range: Opisthokonta, Planctomycetes, Proteobacteria

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

Created 29-Jan-2009 by Caspi R, SRI International


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

Hoshino02: Hoshino T, Sato T (2002). "Squalene-hopene cyclase: catalytic mechanism and substrate recognition." Chem Commun (Camb) (4);291-301. PMID: 12120044

Kohl83: Kohl, W., Gloe, A., Reichenbach, H. (1983). "Steroids from the myxobacterium Nannocystis exedens." Journal of General Microbiology 129(6): 1629-1635.

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

Schouten00: Schouten S, Bowman JP, Rijpstra WI, Sinninghe Damste JS (2000). "Sterols in a psychrophilic methanotroph, Methylosphaera hansonii." FEMS Microbiol Lett 186(2);193-5. PMID: 10802170

Yoder05: Yoder RA, Johnston JN (2005). "A case study in biomimetic total synthesis: polyolefin carbocyclizations to terpenes and steroids." Chem Rev 105(12);4730-56. PMID: 16351060

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

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

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

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

Sung95: Sung CK, Shibuya M, Sankawa U, Ebizuka Y (1995). "Molecular cloning of cDNA encoding human lanosterol synthase." Biol Pharm Bull 18(10);1459-61. PMID: 8593458

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

Young96: Young M, Chen H, Lalioti MD, Antonarakis SE (1996). "The human lanosterol synthase gene maps to chromosome 21q22.3." Hum Genet 97(5);620-4. PMID: 8655142

Report Errors or Provide Feedback
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, biocyc13.