Entry
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
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
Orthology
K14178 amorpha-4,11-diene synthase
Reference
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
Sequence
Reference
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
Sequence
Reference
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
Reference
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
Sequence
Reference
Authors
Martin VJ, Pitera DJ, Withers ST, Newman JD, Keasling JD.
Title
Engineering a mevalonate pathway in Escherichia coli for production of terpenoids.
Journal
Reference
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
Other DBs
ExplorEnz - The Enzyme Database: 4.2.3.24
ExPASy - ENZYME nomenclature database: 4.2.3.24