Toni Kutchan

Prior to joining the Danforth Center in 2006, Dr. Kutchan spent 20 years researching biochemistry at the University of Munich and the Leibniz Institute of Plant Biochemistry in Germany. She is currently investigating how plants produce medicinal compounds at the enzyme and gene level, which could lead to new sources of medications for use against conditions such as chronic pain and cancer. Dr. Kutchan serves as Adjunct Professor of Biology at Washington University. She received her B.S. in Chemistry at the Illinois Institute of Technology and her Ph.D. in Biochemistry at St. Louis University.

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Publications of Drs. Toni Kutchan & Meinhart Zenk

Dr. Toni Kutchan's Publications

Díaz Chávez, M.L., Rolf, M., Gesell, A., and Kutchan, T.M. (2011). Characterization of two methylenedioxy bridge-forming cytochrome P450-dependent enzymes of alkaloid formation in the Mexican prickly poppy Argemone mexicana. Arch. Biochem. Biophys. 507, 186-193. | PubMed| Request Copy |

Dittrich, H., and Kutchan, T.M. (1991). Molecular cloning, expression, and induction of berberine bridge enzyme, an enzyme essential to the formation of benzophenanthridine alkaloids in the response of plants to pathogenic attack. Proc. Natl. Acad. Sci. USA 88, 9969-9973.
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Frick, S., Kramell, R., and Kutchan, T.M. (2007). Metabolic engineering with a morphine biosynthetic P450 in opium poppy surpasses breeding. Metab. Eng. 9, 169-176.
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Gesell, A., Díaz Chávez, M.L., Kramell, R., Piotrowski, M., Macheroux, P., and Kutchan, T.M. (2011). Heterologous expression of two FAD-dependent oxydases with (S)-tetrahydroprotoberberine oxidase activity from Argemone mexicana and Berberis wilsoniae in insect cells. Planta, doi:10.1007/s00425-011-1357-00424.
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Gesell, A., Rolf, M., Ziegler, J., Díaz Chávez, M.L., Huang, F.C., and Kutchan, T.M. (2009). CYP719B1 is salutaridine synthase, the C-C phenol-coupling enzyme of morphine biosynthesis in opium poppy. J. Biol. Chem. 284, 24432-24442.
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Grobe, N., Ren, X., Kutchan, T.M., and Zenk, M.H. (2011). An (R)-specific N-methyltransferase involved in human morphine biosynthesis. Arch. Biochem. Biophys. 506, 42-47.
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Grobe, N., Zhang, B., Fisinger, U., Kutchan, T.M., Zenk, M.H., and Guengerich, F.P. (2009). Mammalian cytochrome P450 enzymes catalyze the phenol-coupling step in endogenous morphine biosynthesis. J. Biol. Chem. 284, 24425-24431.
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Grothe, T., Lenz, R., and Kutchan, T.M. (2001). Molecular characterization of the salutaridinol 7-O-acetyltransferase involved in morphine biosynthesis in opium poppy Papaver somniferum. J. Biol. Chem. 276, 30717-30723.
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Higashi, Y., Kutchan, T.M., and Smith, T.J. (2011). Atomic Structure of Salutaridine Reductase from the Opium Poppy (Papaver somniferum). J. Biol. Chem. 286, 6532-6541.
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Higashi, Y., Smith, T.J., Jez, J.M., and Kutchan, T.M. (2010). Crystallization and preliminary X-ray diffraction analysis of salutaridine reductase from the opium poppy Papaver somniferum. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 66, 163-166.
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Jindaprasert, A., Springob, K., Schmidt, J., De-Eknamkul, W., and Kutchan, T.M. (2008). Pyrone polyketides synthesized by a type III polyketide synthase from Drosophyllum lusitanicum. Phytochemistry 69, 3043-3053.
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Kempe, K., Higashi, Y., Frick, S., Sabarna, K., and Kutchan, T.M. (2009). RNAi suppression of the morphine biosynthetic gene salAT and evidence of association of pathway enzymes. Phytochemistry 70, 579-589.
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Kraus, P.F., and Kutchan, T.M. (1995). Molecular cloning and heterologous expression of a cDNA encoding berbamunine synthase, a C-O phenol-coupling cytochrome P450 from the higher plant Berberis stolonifera. Proc. Natl. Acad. Sci. USA 92, 2071-2075.
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Kutchan, T.M., and Dittrich, H. (1995). Characterization and mechanism of the berberine bridge enzyme, a covalently flavinylated oxidase of benzophenanthridine alkaloid biosynthesis in plants. J. Biol. Chem. 270, 24475-24481.
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Kutchan, T.M., Hampp, N., Lottspeich, F., Beyreuther, K., and Zenk, M.H. (1988). The cDNA clone for strictosidine synthase from Rauvolfia serpentina - DNA sequence determination and expression in  Escherichia coli. FEBS Lett. 237, 40-44.
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Larkin, P.J., Miller, J.A., Allen, R.S., Chitty, J.A., Gerlach, W.L., Frick, S., Kutchan, T.M., and Fist, A.J. (2007). Increasing morphinan alkaloid production by over-expressing codeinone reductase in transgenic Papaver somniferum. Plant Biotech. J. 5, 26-37.
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Nomura, T., and Kutchan, T.M. (2010). Three new O-methyltransferases are sufficient for all O-methylation reactions of Ipecac alkaloid biosynthesis in root culture of Psychotria ipecacuanha. J. Biol. Chem. 285, 7722-7738.
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Nomura, T., and Kutchan, T.M. (2010). Is a metabolic enzyme complex involved in the efficient and accurate control of ipecac alkaloid biosynthesis in Psychotria ipecacuanha? Plant Signal. Behavior 5, 875-877.
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Nomura, T., Quesada, A.L., and Kutchan, T.M. (2008). The new beta-D-Glucosidase in terpenoid-isoquinoline alkaloid biosynthesis in Psychotria ipecacuanha. J. Biol. Chem. 283, 34650-34659.
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Pauli, H.H., and Kutchan, T.M. (1998). Molecular cloning and functional heterologous expression of two alleles encoding (S)-N-methylcoclaurine 3 '-hydroxylase (CYP80B1), a new methyl jasmonate-inducible cytochrome P-450-dependent mono-oxygenase of benzylisoquinoline alkaloid biosynthesis. Plant J. 13, 793-801.
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Springob, K., Samappito, S., Jindaprasert, A., Schmidt, J., Page, J.E., De-Eknamkul, W., and Kutchan, T.M. (2007). A polyketide synthase of Plumbago indica that catalyzes the formation of hexaketide pyrones. FEBS J. 274, 406-417.
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Unterlinner, B., Lenz, R., and Kutchan, T.M. (1999). Molecular cloning and functional expression of codeinone reductase: the penultimate enzyme in morphine biosynthesis in the opium poppy Papaver somniferum. Plant J. 18, 465-475.
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Weid, M., Ziegler, J., and Kutchan, T.M. (2004). The roles of latex and the vascular bundle in morphine biosynthesis in the opium poppy, Papaver somniferum. Proc. Natl. Acad. Sci. USA 101, 13957-13962.
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Winkler, A., Hartner, F., Kutchan, T.M., Glieder, A., and Macheroux, P. (2006). Biochemical evidence that berberine bridge enzyme belongs to a novel family of flavoproteins containing a bi-covalently attached FAD cofactor. J. Biol. Chem. 281, 21276-21285.
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Winkler, A., Kutchan, T.M., and Macheroux, P. (2007). 6-S-cysteinylation of bi-covalently attached FAD in berberine bridge enzyme tunes the redox potential for optimal activity. J. Biol. Chem. 282, 24437-24443.
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Winkler, A., Łyskowski, A., Riedl, S., Puhl, M., Kutchan, T.M., Macheroux, P., and Gruber, K. (2008). A concerted mechanism for berberine bridge enzyme. Nat. Chem. Biol. 4, 739-741.
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Ziegler, J., Díaz Chávez, M., Kramell, R., Ammer, C., and Kutchan, T.M. (2005). Comparative macroarray analysis of morphine containing Papaver somniferum and eight morphine free Papaver species identifies an O-methyltransferase involved in benzylisoquinoline biosynthesis. Planta 222, 458-471.
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Ziegler, J., Voigtländer, S., Schmidt, J., Kramell, R., Miersch, O., Ammer, C., Gesell, A., and Kutchan, T.M. (2006). Comparative transcript and alkaloid profiling in Papaver species identifies a short chain dehydrogenase/reductase involved in morphine biosynthesis. Plant J. 48, 177-192.
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Dr. Meinhart Zenk's Publications

Boettcher, C., Fellermeier, M., Boettcher, C., Dräger, B., and Zenk, M.H. (2005). How human neuroblastoma cells make morphine. Proc. Natl. Acad. Sci. USA 102, 8495-9500.
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Eisenreich, W., Schwarz, M., Cartayrade, A., Arigoni, D., Zenk, M.H., and Bacher, A. (1998). The deoxyxylulose phosphate pathway of terpenoid biosynthesis in plants and microorganisms. Chem. Biol. 5, R221-R233.
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Frölich, N., Dees, C., Paetz, C., Ren, X., Lohse, M.J., Nikolaev, V.O., and Zenk, M.H. (2011). Distinct pharmacological properties of morphine metabolites at G(i)-protein and β-arrestin signaling pathways activated by the human μ-opioid receptor. Biochem. Pharmacol., doi:10.1016/j.bcp.2011.03.001.
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Grill, E., Winnacker, E.L., and Zenk, M.H. (1985). Phytochelatins: the principal heavy-metal complexing peptides of higher plants. Science 230, 674-676.
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Grobe, N., Lamshöft, M., Orth, R.G., Drager, B., Kutchan, T.M., Zenk, M.H., and Spiteller, M. (2010). Urinary excretion of morphine and biosynthetic precursors in mice. Proc. Natl. Acad. Sci. USA 107, 8147-8152.
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Grobe, N., Ren, X., Kutchan, T.M., and Zenk, M.H. (2011). An (R)-specific N-methyltransferase involved in human morphine biosynthesis. Arch. Biochem. Biophys. 506, 42-47.
| PubMed | Request Copy |

Grobe, N., Zhang, B., Fisinger, U., Kutchan, T.M., Zenk, M.H., and Guengerich, F.P. (2009). Mammalian cytochrome P450 enzymes catalyze the phenol-coupling step in endogenous morphine biosynthesis. J. Biol. Chem. 284, 24425-24431
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Gundlach, H., Müller, M.J., Kutchan, T.M., and Zenk, M.H. (1992). Jasmonic acid is a signal transducer in elicitor-induced plant cell cultures. Proc. Natl. Acad. Sci. USA 89, 2389-2393.
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Han, X., Lamshöft, M., Grobe, N., Ren, X.A., Fist, A.J., Kutchan, T.M., Spiteller, M., and Zenk, M.H. (2010). The biosynthesis of papaverine proceeds via (S)-reticuline. Phytochemistry 71, 1305-1312.
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Lenz, R., and Zenk, M.H. (1995). Acetyl coenzyme A:salutaridinol-7-O-acetyltransferase from Papaver somniferum plant cell cultures - The enzyme catalyzing the formation of thebaine in morphine biosynthesis. J. Biol. Chem. 270, 31091-31096.
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Lotter, H., Gollwitzer, J., and Zenk, M.H. (1992). Revision of the configuration at C-7 of salutaridinol-I, the natural intermediate in morphine biosynthesis. Tetrahedron Lett. 33, 2443-2446.
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Nagakura, N., Rueffer, M., and Zenk, M.H. (1979). The biosynthesis of monoterpenoid indole alkaloids from strictosidine. J. C. S. Perkin  I, 2308-2312.
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Nikolaev, V.O., Boettcher, C., Dees, C., Bünemann, M., Lohse, M.J., and Zenk, M.H. (2007). Live cell monitoring of µ-opioid receptor-mediated G-protein activation reveals strong biological activity of close morphine biosynthetic precursors. J. Biol. Chem. 282, 27126-27132.
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Poeaknapo, C., Schmidt, J., Brandsch, M., Dräger, B., and Zenk, M.H. (2004). Endogenous formation of morphine in human cells. Proc. Natl. Acad. Sci. USA 101, 14091-14096.
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Raith, K., Neubert, R., Poeaknapo, C., Boettcher, C., Schmidt, J., and Zenk, M.H. (2003). Electrospray tandem mass spectrometric investigations of morphinans. Am. Soc. Mass Spectr. 14, 1262-1269.
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Schmidt, J., Boettcher, C., Kuhnt, C., Kutchan, T.M., and Zenk, M.H. (2007). Poppy alkaloid profiling by electrospray tandem mass spectrometry and electrospray FT-ICR mass spectrometry after [ring-¹³C₆]-tyramine feeding. Phytochemistry 68, 189-202.
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Stadler, R., and Zenk, M.H. (1990). A revision of the generally accepted pathway for the biosynthesis of the benzyltetrahydroisoquinoline alkaloid reticuline. Liebigs Ann. Chem. 1990, 555-562.
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Streber, W.R., Timmis, K.N., and Zenk, M.H. (1987). Analysis, cloning, and high-level expression of 2,4-dichlorophenoxyacetate monooxygenase gene tfdA of Alcaligenes eutrophus JMP134. J. Bacteriol. 169, 2950-2955.
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Zenk, M.H. (1996). Heavy metal detoxification in higher plants - a review. Gene 179, 21-30.
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Zenk, M.H., Gerardy, R., and Stadler, R. (1989). Phenol oxidative coupling of benzylisoquinoline alkaloids is catalyzed by region- and stereo-selective cytochrome P450 linked plant enzymes: salutaridine and berbamunine. J. Chem. Soc., Chem. Commun. 22, 1725-1727.
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Zenk, M.H., and Juenger, M. (2007). Evolution and current status of the phytochemistry of nitrogenous compounds. Phytochemistry 68,2757-2772.
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