Reaction: geranylgeranyl diphosphate = taxa-4,11-diene + diphosphate
For reaction pathway click here.
Systematic name: geranylgeranyl-diphosphate diphosphate-lyase (cyclizing, taxadiene-forming)
Other name(s): geranylgeranyl-diphosphate diphosphate-lyase (cyclizing, taxadiene-forming)
Systematic name: geranylgeranyl-diphosphate diphosphate-lyase (cyclizing; taxa-4,11-diene-forming)
Comments: This is the committed step in the biosynthesis of the diterpenoid antineoplastic drug taxol (paclitaxel). The cyclization involves a 1,5-hydride shift.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 169277-52-5
References:
1. Koepp, A.E., Hezari, M., Zajicek, J., Vogel, B.S., LaFever, R.E., Lewis, N.G. and Croteau, R. Cyclization of geranylgeranyl diphosphate to taxa-4(5),11(12)-diene is the committed step of taxol biosynthesis in Pacific yew. J. Biol. Chem. 270 (1995) 8686-8690. [PMID: 7721772]
2. Hezari, M., Lewis, N.G. and Croteau, R. Purification and characterization of taxa-4(5),11(12)-diene synthase from Pacific yew (Taxus brevifolia) that catalyzes the first committed step of taxol biosynthesis. Arch. Biochem. Biophys. 322 (1995) 437-444. [PMID: 7574719]
3. Lin, X., Hezari, M., Koepp, A.E., Floss, H.G. and Croteau, R. Mechanism of taxadiene synthase, a diterpene cyclase that catalyzes the first step of taxol biosynthesis in Pacific yew. Biochemistry 35 (1996) 2968-2977. [PMID: 8608134]
4. Hezari, M., Ketchum, R.E., Gibson, D.M. and Croteau, R. Taxol production and taxadiene synthase activity in Taxus canadensis cell suspension cultures. Arch. Biochem. Biophys. 337 (1997) 185-90. [PMID: 9016812]
5. Williams, D.C., Carroll, B.J., Jin, Q., Rithner, C.D., Lenger, S.R., Floss, H.G., Coates, R.M., Williams, R.M. and Croteau, R. Intramolecular proton transfer in the cyclization of geranylgeranyl diphosphate to the taxadiene precursor of taxol catalyzed by recombinant taxadiene synthase. Chem. Biol. 7 (2000) 969-977. [PMID: 11137819]