KEGG   ENZYME: 4.2.3.24Help
Entry
EC 4.2.3.24                 Enzyme                                 

Name
amorpha-4,11-diene synthase;
amorphadiene synthase
Class
Lyases;
Carbon-oxygen lyases;
Acting on phosphates
BRITE hierarchy
Sysname
(2E,6E)-farnesyl-diphosphate diphosphate-lyase (amorpha-4,11-diene-forming)
Reaction(IUBMB)
(2E,6E)-farnesyl diphosphate = amorpha-4,11-diene + diphosphate [RN:R07630]
Reaction(KEGG)
Substrate
(2E,6E)-farnesyl diphosphate [CPD:C00448]
Product
amorpha-4,11-diene [CPD:C16028];
diphosphate [CPD:C00013]
Comment
Requires Mg2+ and Mn2+ for activity. This is a key enzyme in the biosynthesis of the antimalarial endoperoxide artemisinin [3]. Catalyses the formation of both olefinic [e.g. amorpha-4,11-diene, amorpha-4,7(11)-diene, gamma-humulene and beta-sesquiphellandrene] and oxygenated (e.g. amorpha-4-en-7-ol) sesquiterpenes, with amorpha-4,11-diene being the major product. When geranyl diphosphate is used as a substrate, no monoterpenes are produced [2].
History
EC 4.2.3.24 created 2006
Pathway
ec00909  Sesquiterpenoid and triterpenoid biosynthesis
ec01110  Biosynthesis of secondary metabolites
ec01130  Biosynthesis of antibiotics
Orthology
K14178  amorpha-4,11-diene synthase
Reference
1  [PMID:11289612]
  Authors
Wallaart TE, Bouwmeester HJ, Hille J, Poppinga L, Maijers NC.
  Title
Amorpha-4,11-diene synthase: cloning and functional expression of a key enzyme in the biosynthetic pathway of the novel antimalarial drug artemisinin.
  Journal
Planta 212:460-5 (2001)
DOI:10.1007/s004250000428
  Sequence
Reference
2  [PMID:11032404]
  Authors
Mercke P, Bengtsson M, Bouwmeester HJ, Posthumus MA, Brodelius PE.
  Title
Molecular cloning, expression, and characterization of amorpha-4,11-diene synthase, a key enzyme of artemisinin biosynthesis in Artemisia annua L.
  Journal
Arch Biochem Biophys 381:173-80 (2000)
DOI:10.1006/abbi.2000.1962
  Sequence
Reference
3  [PMID:10626375]
  Authors
Bouwmeester HJ, Wallaart TE, Janssen MH, van Loo B, Jansen BJ, Posthumus MA, Schmidt CO, De Kraker JW, Konig WA, Franssen MC.
  Title
Amorpha-4,11-diene synthase catalyses the first probable step in artemisinin biosynthesis.
  Journal
Phytochemistry 52:843-54 (1999)
DOI:10.1016/S0031-9422(99)00206-X
Reference
4  [PMID:11185551]
  Authors
Chang YJ, Song SH, Park SH, Kim SU.
  Title
Amorpha-4,11-diene synthase of Artemisia annua: cDNA isolation and bacterial expression of a terpene synthase involved in artemisinin biosynthesis.
  Journal
Arch Biochem Biophys 383:178-84 (2000)
DOI:10.1006/abbi.2000.2061
  Sequence
Reference
5  [PMID:12778056]
  Authors
Martin VJ, Pitera DJ, Withers ST, Newman JD, Keasling JD.
  Title
Engineering a mevalonate pathway in Escherichia coli for production of terpenoids.
  Journal
Nat Biotechnol 21:796-802 (2003)
DOI:10.1038/nbt833
Reference
6  [PMID:16143293]
  Authors
Picaud S, Mercke P, He X, Sterner O, Brodelius M, Cane DE, Brodelius PE.
  Title
Amorpha-4,11-diene synthase: mechanism and stereochemistry of the enzymatic cyclization of farnesyl diphosphate.
  Journal
Arch Biochem Biophys 448:150-5 (2006)
DOI:10.1016/j.abb.2005.07.015
Other DBs
ExplorEnz - The Enzyme Database: 4.2.3.24
IUBMB Enzyme Nomenclature: 4.2.3.24
ExPASy - ENZYME nomenclature database: 4.2.3.24
BRENDA, the Enzyme Database: 4.2.3.24
CAS: 259213-60-0

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