Reaction: (19E)-geissoschizine + O2 + [reduced NADPH-hemoprotein reductase] = akuammicine + formate + H2O + [oxidized NADPH-hemoprotein reductase] (overall reaction)
(1a) (19E)-geissoschizine + O2 + [reduced NADPH-hemoprotein reductase] = 3,17-didehydrostemmadenine + 2 H2O + [oxidized NADPH-hemoprotein reductase]
(1b) 3,17-didehydrostemmadenine = 17-dehydropreakuammicine (spontaneous)
(1c) 17-dehydropreakuammicine + H2O = 17-dehydropreakuammicine hydrate (spontaneous)
(1d) 17-dehydropreakuammicine hydrate = akuammicine + formate (spontaneous)
For diagram of reaction, click here and mechanism click here
Glossary: (19E)-geissoschizine = methyl (16ξ,19E)-16-formylcoryn-19-en-17-oate
Other name(s): GO (gene name); CYP71D1V1 (gene name)
Systematic name: (19E)-geissoschizine,[reduced NADPH-hemoprotein reductase]:oxygen oxidoreductase (akuammicine-forming)
Comments: A cytochrome P-450 (heme-thiolate) enzyme characterized from the plant Catharanthus roseus (Madagascar periwinkle), that participates in the biosynthesis of a number of monoterpene alkaloids, as well as the bisindole alkaloids vinblastine and vincristine. The enzyme generates a nine-carbon ring that contains a nitrogen atom. The direct product of the enzyme, 3,17-didehydrostemmadenine, is unstable, and in the absence of other enzymes becomes akuammicine non-enzymically. However, in the presence of two dehydrogenases it is converted to stemmadenine via 17-dehydrostemmadenine.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Tatsis, E.C., Carqueijeiro, I., Duge de Bernonville, T., Franke, J., Dang, T.T., Oudin, A., Lanoue, A., Lafontaine, F., Stavrinides, A.K., Clastre, M., Courdavault, V. and O'Connor, S.E. A three enzyme system to generate the Strychnos alkaloid scaffold from a central biosynthetic intermediate. Nat. Commun. 8 (2017) 316. [PMID: 28827772]
2. Qu, Y., Easson, M.EA.M., Simionescu, R., Hajicek, J., Thamm, A.MK., Salim, V. and De Luca, V. Solution of the multistep pathway for assembly of corynanthean, strychnos, iboga, and aspidosperma monoterpenoid indole alkaloids from 19E-geissoschizine. Proc. Natl. Acad. Sci. USA 115 (2018) 3180-3185. [PMID: 29511102]
3. Salim, V., Jarecki, S.A., Vick, M. and Miller, R. Advances in metabolic engineering of plant monoterpene indole alkaloids. Biology (Basel) 12 (2023) . [PMID: 37626942]