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Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
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MetaCyc Enzyme: amorpha-4,11-diene synthase

Gene: kcs12 Accession Number: G-9421 (MetaCyc)

Species: Artemisia annua

Molecular Weight of Polypeptide: 63.5 kD (from nucleotide sequence)

Unification Links: Entrez:CAB94691 , Protein Model Portal:Q9AR04 , UniProt:Q9AR04

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

Gene-Reaction Schematic: ?


Enzymatic reaction of: amorpha-4,11-diene synthase

EC Number: 4.2.3.24

(2E,6E)-farnesyl diphosphate <=> amorpha-4,11-diene + diphosphate

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

In Pathways: artemisinin biosynthesis

Summary:
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

Activators (Unknown Mechanism): Mg2+ [Chang00]


References

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


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 SRI International Pathway Tools version 18.5 on Sun Dec 21, 2014, biocyc11.