Reaction: (2E,6E)-farnesyl diphosphate = amorpha-4,11-diene + diphosphate
For diagram of reaction click here and mechanism click here.
Other name(s): amorphadiene synthase; 2-trans,6-trans-farnesyl-diphosphate diphosphate-lyase (amorpha-4,11-diene-forming)
Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase (amorpha-4,11-diene-forming)
Comments: 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, γ-humulene and β-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].
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 259213-60-0
References:
1. Wallaart, T.E., Bouwmeester, H.J., Hille, J., Poppinga, L. and Maijers, N.C. 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 (2001) 460-465. [PMID: 11289612]
2. Mercke, P., Bengtsson, M., Bouwmeester, H.J., Posthumus, M.A. and Brodelius, P.E. Molecular cloning, expression, and characterization of amorpha-4,11-diene synthase, a key enzyme of artemisinin biosynthesis in Artemisia annua L. Arch. Biochem. Biophys. 381 (2000) 173-180. [PMID: 11032404]
3. Bouwmeester, H.J., Wallaart, T.E., Janssen, M.H., van Loo, B., Jansen, B.J., Posthumus, M.A., Schmidt, C.O., De Kraker, J.W., Konig, W.A. and Franssen, M.C. Amorpha-4,11-diene synthase catalyses the first probable step in artemisinin biosynthesis. Phytochemistry 52 (1999) 843-854. [PMID: 10626375]
4. Chang, Y.J., Song, S.H., Park, S.H. and Kim, S.U. 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 (2000) 178-184. [PMID: 11185551]
5. Martin, V.J., Pitera, D.J., Withers, S.T., Newman, J.D. and Keasling, J.D. Engineering a mevalonate pathway in Escherichia coli for production of terpenoids. Nat. Biotechnol. 21 (2003) 796-802. [PMID: 12778056]
6. Picaud, S., Mercke, P., He, X., Sterner, O., Brodelius, M., Cane, D.E. and Brodelius, P.E. Amorpha-4,11-diene synthase: Mechanism and stereochemistry of the enzymatic cyclization of farnesyl diphosphate. Arch. Biochem. Biophys. 448 (2006) 150-155. [PMID: 16143293]