|Gene:||kcs12||Accession Number: G-9421 (MetaCyc)|
Species: Artemisia annua
Molecular Weight of Polypeptide: 63.5 kD (from nucleotide sequence)
Relationship Links: Entrez-Nucleotide:PART-OF:AJ251751 , InterPro:IN-FAMILY:IPR001906 , InterPro:IN-FAMILY:IPR005630 , InterPro:IN-FAMILY:IPR008930 , InterPro:IN-FAMILY:IPR008949 , Pfam:IN-FAMILY:PF01397 , Pfam:IN-FAMILY:PF03936
Enzymatic reaction of: amorpha-4,11-diene synthase
EC Number: 18.104.22.168
The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.
The reaction is physiologically favored in the direction shown.
In Pathways: artemisinin biosynthesis
The cDNA encoding amorpha-4,11-diene synthase (ADS) was isolated from Artemisia annua and its molecular function to cyclisize farnesyl diphosphate (FDP) forming amorpha-4,11-diene confirmed by heterologous expression in E. coli [Chang00]. The enzyme requires a divalent metalion and prefers Mg2+. The function of ADS has also been confirmed in transformed tobacco [Wallaart01].
The reaction sequence has been shown to involve the following steps [Picaud05]:
1) ionization of FDP to form nerolidyl diphosphate (NPP)
2) ionization of NPP followed by 1,6-ring closure to generate the bisabolyl cation
3) 1,3-hydride shift of the bisabolyl cation to yield a cationic intermediate
4) 1,10-closure to generate the amorphane skeleton
5) deprotonation at either C12 or C13 of the amorphyl cation to produce amorpha-4,11-diene
Chang00: Chang YJ, Song SH, Park SH, Kim SU (2000). "Amorpha-4,11-diene synthase of Artemisia annua: cDNA isolation and bacterial expression of a terpene synthase involved in artemisinin biosynthesis." Arch Biochem Biophys 383(2);178-84. PMID: 11185551
Picaud05: Picaud S, Olofsson L, Brodelius M, Brodelius PE (2005). "Expression, purification, and characterization of recombinant amorpha-4,11-diene synthase from Artemisia annua L." Arch Biochem Biophys 436(2);215-26. PMID: 15797234
Wallaart01: Wallaart TE, Bouwmeester HJ, Hille J, Poppinga L, Maijers NC (2001). "Amorpha-4,11-diene synthase: cloning and functional expression of a key enzyme in the biosynthetic pathway of the novel antimalarial drug artemisinin." Planta 212(3);460-5. PMID: 11289612
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