Metabolic Modeling Tutorial
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Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
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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 [Chang00a]. 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+ [Chang00a]


References

Chang00a: 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 Thu Nov 27, 2014, BIOCYC14B.