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Journal of the American Chemical Society
Toxicol. 2016, 16 (1), 14–22.
ASSOCIATED CONTENT
Supporting Information. Materials and Methods, Figures S1-
S20, Tables S1-S3, Data S1, References (1-6). This material is
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Caputi, L.; Franke, J.; Farrow, S. C.; Chung, K.; Payne, R. M. E.;
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Enzymes in the Biosynthesis of the Anticancer Drug
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AUTHOR INFORMATION
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Farrow, S. C.; Kamileen, M. O.; Meades, J.; Ameyaw, B.; Xiao,
Y.; O’Connor, S. E. Cytochrome P450 and O-
Methyltransferase Catalyze the Final Steps in the
Biosynthesis of the Anti-Addictive Alkaloid Ibogaine from
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Corresponding Author
*Correspondence to: oconnor@ice.mpg.de
Funding Sources
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We acknowledge ERC 788301 (S.E.O.), EMBO ALTF 846-2016
(S.C.F), NSF Graduate Fellowship (DGE 1256260) (R.C.M.).
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Notes
Authors declare no competing interests. All data is available in
the main text or the supplementary materials. Genbank
accession numbers: MK840850 (TiPAS1); MK840851
(TiPAS2); MK840852 (TiPAS3); MK840853 (TiTabS);
MK840854 (TiCorS); MK840855 (TiDPAS1); MK840856
(TiDPAS2); MK840857 (TiPNAE1); MK840858 (TiPNAE2);
MK840859 (TiPNAE3).
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ACKNOWLEDGMENT
We gratefully acknowledge Dr. Kenneth Alper for introduction
to this compound, and to Jonathan Dickerson of the Ibogaine
Alliance for seeds. We thank Jakob Franke, Benjamin Lichman
and Matthew DeMars for intellectual contributions, Gerhard
Saalbach and Carlo de-Oliveira-Martins for protein mass
spectrometry and David Lawson and Clare Stevenson for
helpful discussions. We thank Andrew Davis (John Innes
Centre) for the photograph of Iboga in the graphical abstract.
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Stout, D. M.; Meyers, A. I. Recent Advances in the Chemistry
of Dihydropyridines. Chem. Rev. 1982, 82 (2), 223–243.
Buonora, P.; Olsen, J.-C.; Oh, T. Recent Developments in
Imino Diels–Alder Reactions. Tetrahedron 2001, 57 (29),
6099–6138.
ABBREVIATIONS
Catharanthus roseus catharanthine synthase, CrCS;
Tabernanthe iboga coronaridine synthase, TiCorS;
Tabernanthe iboga dihydroprecondylocarpine acetate
synthase 1, TiDPAS1; Tabernanthe iboga
dihydroprecondylocarpine acetate synthase 2, TiDPAS2; flavin
adenine dinucleotide, FAD; nicotinamide adenine dinucleotide
phosphate, NADPH; Tabernanthe iboga polyneudridine
aldehyde esterase like 1, TiPNAE1; Tabernanthe iboga
polyneudridine aldehyde esterase like 2, TiPNAE2;
Tabernanthe iboga polyneudridine aldehyde esterase like 3,
TiPNAE3; Tabernanthe iboga precondylocarpine acetate
synthase 1, TiPAS1; Tabernanthe iboga precondylocarpine
acetate synthase 2, TiPAS2; Tabernanthe iboga
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Jenks, C. Voacanga Extraction Manual Phase 4ꢀ: Production
and Purification. 2015, 1–26.
Dogru, E.; Warzecha, H.; Seibel, F.; Haebel, S.; Lottspeich, F.;
Stöckigt, J. The Gene Encoding Polyneuridine Aldehyde
Esterase of Monoterpenoid Indole Alkaloid Biosynthesis in
Plants Is an Ortholog of the α/β Hydrolase Super Family. Eur.
J. Biochem. 2000, 267 (5), 1397–1406.
Seong, S.; Lim, H.; Han, S. Biosynthetically Inspired
Transformation of Iboga to Monomeric Post-Iboga Alkaloids.
Chem 2019, 5 (2), 353–363.
Berrow, N. S.; Alderton, D.; Sainsbury, S.; Nettleship, J.;
Assenberg, R.; Rahman, N.; Stuart, D. I.; Owens, R. J. A
Versatile Ligation-Independent Cloning Method Suitable for
High-Throughput Expression Screening Applications. Nucleic
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Shevchenko, A.; Tomas, H.; Havli, J.; Olsen, J. V.; Mann, M. In-
Gel Digestion for Mass Spectrometric Characterization of
Proteins and Proteomes. Nat. Protoc. 2006, 1 (6), 2856–
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Accuracies and Proteome-Wide Protein Quantification. Nat.
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precondylocarpine acetate synthase 3, TiPAS3; Tabernanthe
iboga tabersonine synthase, TiTabS; Catharanthus roseus
tabersonine synthase, CrTS.
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